Prosthetic valve and upstream support therefor

ABSTRACT

Apparatus is provided, including: (A) a valve body ( 204 ) including a first frame ( 206 ) shaped to define a lumen therethrough, and a valve member ( 205 ) disposed within the lumen, (B) an upstream support ( 210 ), configured to be placed against an upstream surface of a native heart valve, and (C) a flexible sheet ( 214 ) that couples the upstream support to the valve body. The valve body has a compressed state in which the first frame has a first diameter, and an expanded state in which the first frame has a second diameter that is greater than the first diameter. The support includes a second frame ( 212 ) that has a compressed state, and an expanded state in which the second frame is annular, has an inner perimeter that defines an opening through the second frame, and has an outer perimeter. Other embodiments are also described.

CROSS-REFERENCES TO RELATED APPLICATIONS

The present application is a Continuation of U.S. patent applicationSer. No. 15/872,501 to Hammer et al., entitled “Prosthetic valve andupstream support therefor,” which published as US 2018/0147059, andwhich is a Continuation of U.S. patent application Ser. No. 14/763,004to Hammer et al., entitled “Ventricularly-anchored prosthetic valves,”which published as US 2015/0351906, and which is the US National Phaseof PCT application IL2014/050087 to Hammer et al., filed Jan. 23, 2014,and entitled “Ventricularly-anchored prosthetic valves,” which publishedas WO 2014/115149, and which:

-   -   claims priority from (i) U.S. provisional patent application        61/756,049 to HaCohen et al., filed Jan. 24, 2013, and entitled        “Ventricularly-anchored prosthetic valve support”; and (ii) U.S.        provisional patent application 61/756,034 to HaCohen et al.,        filed Jan. 24, 2013, and entitled “Tissue-engaging elements”,        and    -   is related to:

US patent application publication 2012/0022639 to Hacohen et al., filedJul. 21, 2010 (now U.S. Pat. No. 9,132,009);

US patent application publication 2012/0022640 to Gross et al., filedFeb. 24, 2011 (now U.S. Pat. No. 8,992,604);

U.S. patent application Ser. No. 13/811,308 to Gross et al., filed Jan.21, 2013, which published as US 2013/0172992 (now U.S. Pat. No.9,017,399);

U.S. patent application Ser. No. 13/412,814 to Gross et al., filed Mar.6, 2012, which published as US 2013/0035759 (now U.S. Pat. No.8,852,272);

PCT patent application IL2012/000292 to Gross et al., filed Aug. 5,2012, which published as WO/2013/021374;

PCT patent application IL2012/000293 to Gross et al., filed Aug. 5,2012, which published as WO/2013/021375; and

a US patent application to HaCohen et al., entitled “Anchoring ofprosthetic valve supports”, filed Jan. 23, 2014, which was assignedapplication Ser. No. 14/161,921 (now U.S. Pat. No. 9,681,952),

all of which are incorporated herein by reference.

FIELD OF THE INVENTION

Some applications of the present invention relate in general to valvereplacement. More specifically, some applications of the presentinvention relate to prosthetic cardiac valves and techniques forimplantation thereof.

BACKGROUND

Ischemic heart disease causes regurgitation of a heart valve by thecombination of ischemic dysfunction of the papillary muscles, and thedilatation of the ventricle that is present in ischemic heart disease,with the subsequent displacement of the papillary muscles and thedilatation of the valve annulus.

Dilation of the annulus of the valve prevents the valve leaflets fromfully coapting when the valve is closed. Regurgitation of blood from theventricle into the atrium results in increased total stroke volume anddecreased cardiac output, and ultimate weakening of the ventriclesecondary to a volume overload and a pressure overload of the atrium.

SUMMARY OF THE INVENTION

For some applications of the invention, tissue anchors coupled totethers are transluminally anchored to ventricular tissue of a nativevalve. A prosthetic valve component, such as a prosthetic valveassembly, a prosthetic valve body, or a support, is transluminally slidalong a guide member coupled to the tethers, and is anchored to thetethers.

For some applications, a prosthetic valve assembly comprises (1) a valvebody shaped to define a lumen therethrough, and a valve member disposedwithin the lumen, (2) an upstream support configured to be placedagainst an upstream surface of a native heart valve, and (2) a flexiblesheet that couples the upstream support to the valve body.

For some applications, the prosthetic valve assembly comprises eyeletsto facilitate sliding along the guide member.

For some applications, the prosthetic valve assembly has a compresseddelivery state in which the valve body and the upstream support arearticulatably coupled to each other by the sheet. For such applications,a delivery tool houses the prosthetic valve assembly such that the valvebody and upstream support are articulatable with respect to each otherduring transluminal delivery.

For some applications, the prosthetic valve assembly comprises tethersthat, when tensioned, move the valve body closer to the support. Forsuch applications, the assembly typically comprises tissue-engagingelements that protrude from the valve body, and the tethers aretensioned to sandwich tissue of the native valve between thetissue-engaging elements and the support.

For some applications, one or more forces is measured duringimplantation, and distributed among various anchoring elements. For somesuch applications, an intracorporeal spring is used that isextracorporeally observable using imaging techniques. For some suchapplications, the spring facilitates force distribution.

For some applications, a prosthetic valve assembly comprises a flexiblesheet forms a pocket between the sheet and a frame of the assembly, andfacilitates sealing between the assembly and tissue of the native valve.

For some applications of the invention, tissue anchors coupled tolongitudinal members that are reversibly couplable to wires aretransluminally advanced to the ventricle downstream of a native heartvalve, and are anchored there. A prosthetic valve support comprising anupstream support portion is slid, in a compressed deliveryconfiguration, over the wires and part of each longitudinal member, andinto an atrium upstream of the native valve where it is deployed (e.g.,expanded) and placed against an upstream surface (e.g., an atrialsurface) of the native valve. A locking member is also slid over thewires and part of each longitudinal member, and locks to thelongitudinal member, thereby securing the prosthetic valve supportagainst the upstream surface of the native valve. A prosthetic valve issubsequently transluminally advanced to the native valve, and isimplanted by coupling the prosthetic valve to leaflets of the nativevalve and to the prosthetic valve support.

For some applications of the invention, a tubular member is slidableover the wire and the longitudinal member, and when disposed over thewire and the long member, inhibits decoupling of the wire from thelongitudinal member. For such applications, the prosthetic valve supportand the locking member are typically slidable over the tubular member.

For some applications of the invention, a control rod, reversiblycoupled to the locking member, is slid over the tubular member so as topush the locking member and the prosthetic valve support over thetubular member. For some such applications, the control rod is used tolock the locking member to the longitudinal member.

There is therefore provided, in accordance with an application of thepresent invention, apparatus for use with a native valve of a heart of asubject, the apparatus including:

a valve body:

-   -   including (1) a first frame shaped to define a lumen        therethrough, and (2) a valve member disposed within the lumen,    -   having a compressed state in which the first frame has a first        diameter, and    -   having an expanded state in which the first frame has a second        diameter that is greater than the first diameter;        -   an upstream support:    -   configured to be placed against an upstream surface of the        native valve,    -   including a second frame,        -   having a compressed state, and        -   having an expanded state in which the second frame is            annular, has an inner perimeter that defines an opening            through the second frame, and has an outer perimeter; and

a flexible sheet that couples the upstream support to the valve body.

In an application, the upstream support is coupled to the valve bodyonly via the sheet.

In an application:

the valve body has an upstream end, a downstream end, and a longitudinalaxis therebetween along which the lumen is defined, and

when the valve body is in the expanded state thereof and the upstreamsupport is in the expanded state thereof:

-   -   the first frame is attached to the second frame at the inner        perimeter of the second frame, and    -   the sheet is attached to the valve body and to the upstream        support in a manner that defines a pocket region between the        sheet and at least the inner perimeter of the second frame, the        sheet not being attached to the first frame or the second frame        in the pocket region.

In an application, the sheet provides fluid communication between theopening and the lumen.

In an application, the sheet is not attached to the inner perimeter ofthe second frame.

In an application, the sheet is not attached to an upstream end of thevalve body.

In an application, the sheet is generally annular when the valve body isin the expanded state thereof and the upstream support is in theexpanded state thereof.

In an application, the sheet is generally frustoconical when the valvebody is in the expanded state thereof and the upstream support is in theexpanded state thereof.

In an application, the sheet is attached to the inner perimeter of thesecond frame.

In an application, the sheet is circumferentially attached to the secondframe at a radius that is greater than a radius of the inner perimeter.

In an application, the sheet is circumferentially attached to the secondframe at the outer perimeter of the second frame.

In an application, the sheet is attached to an upstream end of the valvebody.

In an application, the first frame is generally cylindrical in both thecompressed state thereof and the expanded state thereof.

In an application, the second frame is generally cylindrical in thecompressed state thereof.

In an application, the valve body includes at least one downstreamanchor, configured such that, in the expanded configuration of the valvebody, the anchor protrudes radially outward from the first frame.

In an application, the apparatus further includes at least onetensioning element, coupled to the valve body and to the upstreamsupport, a length of the tensioning element between the valve body andthe upstream portion being adjustable such that a distance between thefirst frame and the second frame is adjustable.

In an application, the at least one tensioning element includes atether.

In an application, the at least one tensioning element is coupled to thefirst frame, and slidably coupled to the second frame.

In an application, the valve body, the upstream support and the sheettogether define a prosthetic valve assembly, the prosthetic valveassembly:

having an expanded state in which the valve body is in the expandedstate thereof and the second frame of the upstream support is in theexpanded state thereof,

having a compressed state in which:

-   -   the prosthetic valve assembly has a longitudinal axis,    -   the valve body is in the compressed state thereof at a first        zone of the longitudinal axis,    -   the upstream support is in the compressed state thereof at a        second zone of the longitudinal axis, and    -   the prosthetic valve assembly defines an articulation zone,        between the first zone and the second zone, in which at least        part of the sheet is disposed, in which neither the first frame        nor the second frame is disposed, and about which the valve body        and the upstream support are articulatable with respect to each        other.

In an application, the apparatus further includes a delivery tool:

including a first housing configured to house and maintain at least partof the upstream support in the compressed state thereof, and defining afirst housing orifice through which the at least part of the upstreamsupport is removable from the first housing,

including a second housing configured to house and maintain at leastpart of the valve body in the compressed state thereof, and defining asecond housing orifice through which the at least part of the valve bodyis removable from the second housing,

having a contracted state in which the second housing is disposed at afirst distance from the first housing, and in which the delivery tool isconfigured to transluminally advance the prosthetic valve assembly inthe compressed state thereof, to the native valve, and

having an extended state in which the second housing is disposed at asecond distance from the first housing, the second distance beinggreater than the first distance, and the apparatus is configured suchthat, when the at least part of the upstream support is housed by thefirst housing and the at least part of the valve body is housed by thesecond housing, transitioning of the delivery tool from the contractedstate into the extended state exposes at least part of at least onecomponent selected from the group consisting of: the valve body and theupstream support, from the housing that houses the selected component.

In an application:

the apparatus is configured to be used with at least two guide members,

the prosthetic valve assembly includes at least two eyelets, each eyeletbeing slidable over a respective one of the guide members, and

the apparatus is configured such that the eyelets of the prostheticvalve assembly protrude radially outward and radially beyond an outersurface of the second housing while: (1) the at least part of the valvebody, in the compressed state thereof, is housed by the second housing,and (2) the at least part of the upstream support, in the compressedstate thereof, is housed by the first housing.

In an application, the eyelets are pivotably coupled to the valve body.

In an application, the delivery tool further includes at least tworeference-force tubes, each reference-force tube configured (1) to beslidable over a respective one of the guide members, and (2) to apply adistally-directed force to the prosthetic valve assembly.

In an application, in the compressed state of the prosthetic valveassembly, each reference-force tube extends distally (1) through a lumendefined by the second frame of the upstream support, (2) through thesheet, and (3) along an outside of at least part of the valve body.

In an application, the apparatus further includes at least two lockingmembers, each locking member:

having an unlocked state in which the locking member is slidable along arespective one of the guide members,

being transitionable into a locked state in which (1) the locking memberis locked to the respective one of the guide members, and (2) thesliding of the eyelet over the guide member is inhibited.

In an application, the apparatus further includes the at least two guidemembers:

each guide member includes:

-   -   a tubular member, shaped to define a lumen therethrough,    -   a tether, coupled at a distal end thereof to a tissue anchor        configured to be anchored to ventricular tissue of the heart, at        least a proximal portion of the tether being disposed within the        lumen of the tubular member, and    -   a pull-wire, coupled at a distal portion thereof to the proximal        portion of the tether, at least the distal portion of the        pull-wire being disposed within the lumen of the tubular member,

the tubular member inhibits decoupling of the pull-wire from the tetherwhile the distal portion of the pull-wire and the proximal portion ofthe tether are disposed within the lumen of the tubular member, and

while the tubular member of each guide member is disposed within therespective locking member, the tubular member inhibits transitioning ofthe locking member into the locked state.

In an application, the apparatus is configured such that, for eachrespective guide member and locking member, while (1) the tubular memberis disposed within the locking member, (2) the distal portion of thepull-wire and the proximal portion of the tether are disposed within thelumen of the tubular member, and (3) the tissue anchor is coupled to theventricular tissue:

proximal sliding of the tubular member with respect to the tetherfacilitates automatic transitioning of the locking member into thelocked state, and

further proximal sliding of the tubular member with respect to thetether facilitates decoupling of the pull-wire from the tether.

In an application, at least one housing selected from the groupconsisting of: the first housing and the second housing has a lateralwall that is shaped to define at least two slits, the eyelets beingconfigured to protrude radially outward from the delivery tool via theslits.

In an application, each slit of the at least one selected housing iscontinuous with the orifice of the at least one selected housing.

In an application, the eyelets are coupled to and protrude radiallyoutward from the valve body.

In an application, the eyelets are pivotably coupled to the valve body.

In an application:

the articulation zone defined by the prosthetic valve assembly includesa first articulation zone, and

while (1) the at least part of the valve body, in the compressed statethereof, is housed by the second housing, (2) the at least part of theupstream support, in the compressed state thereof, is housed by thefirst housing, and (3) the delivery tool is in the contracted statethereof, the apparatus defines a second articulation zone at alongitudinal zone of the apparatus (a) between the second housing andthe first housing, and (b) in which is disposed at least part of thefirst articulation zone.

In an application, the delivery tool further includes a housing-controlrod that extends through the first housing and is coupled to the secondhousing such that a first portion of the housing-control rod is disposedwithin the first housing, a second portion of the housing-control rod isdisposed within the second housing, and a third portion of thehousing-control rod (1) is disposed within the second articulation zone,and (2) is more flexible than at least one portion of thehousing-control rod selected from the group consisting of: the firstportion and the second portion.

In an application:

the delivery tool further includes (1) a control rod assembly includingat least a first housing-control rod coupled to the first housing, and(2) a second housing-control rod, more flexible than the firsthousing-control rod, extending through the first housing-control rod,extending through the second articulation zone, and coupled to thesecond housing.

In an application, the second housing orifice faces the first housingorifice.

In an application:

the delivery tool further includes a flexible control rod assemblyincluding (1) a first housing-control rod coupled to the first housing,(2) a second housing-control rod coupled to the second housing, and (3)a prosthesis-control rod reversibly couplable to the prosthetic valveassembly,

longitudinal movement of the second housing-control rod with respect tothe first housing-control rod transitions the delivery tool between thecontracted state and the extended state thereof, and

the valve body is removable from the second housing by moving the secondhousing-control rod with respect to the prosthesis-control rod.

In an application, the prosthesis-control rod is reversibly couplable tothe prosthetic valve assembly by being reversibly couplable to the valvebody.

In an application, at least part of the second housing-control rod isdisposed within and slidable through the prosthesis-control rod, and atleast part of the prosthesis-control rod is disposed within and slidablethrough the first housing-control rod.

In an application, the outer perimeter of the second frame has a thirddiameter that is greater than the second diameter.

In an application, the inner perimeter has a fourth diameter that isgreater than the second diameter.

In an application, when the valve body is in the expanded state thereofand the upstream support is in the expanded state thereof, a gap isdefined between the first frame and the second frame, the sheet spanningthe gap.

In an application, no metallic structure is disposed within the gap.

In an application, the sheet is configured to inhibit expansion of thesecond frame.

In an application, the apparatus is configured such that when the secondframe expands from the compressed state thereof toward the expandedstate thereof, the sheet retains the second frame in a generallyfrustoconical shape by inhibiting expansion of at least the outerperimeter of the second frame.

In an application, the sheet extends over at least part of the secondframe to serve as a covering of the upstream support.

In an application, the covering defines a tissue-contacting surface ofthe upstream support.

In an application, the sheet extends over at least part of the firstframe to serve as a covering of the valve body.

In an application, the covering is disposed on an inner surface of thefirst frame.

There is further provided, in accordance with an application of thepresent invention, apparatus for use with a native valve of a heart of asubject, the apparatus including:

a prosthetic valve, configured to be percutaneously delivered to thenative valve;

an annular upstream support, configured to be placed against an upstreamsurface of the native valve, and to support the prosthetic valve at thenative valve;

a tissue anchor, including a tissue-engaging element configured to beanchored to ventricular muscle tissue of the heart;

a tether, coupled to the tissue anchor; and

a spring, couplable to the tether so as to elastically couple thetissue-engaging element to the prosthetic valve.

In an application, the spring is shaped to define a repeating pattern.

In an application, the spring is pre-loaded.

In an application, the spring is a constant-force spring.

In an application, the spring is configured to facilitate extracorporealfluoroscopic observation of a state of the spring.

In an application, the spring is coupled to a plurality of radiopaquemarkers such that a juxtaposition of the markers changes as the state ofthe spring changes, the juxtaposition of the markers beingextracorporeally fluoroscopically observable.

In an application, the spring is coupled to at least one radiopaquemarker, and the apparatus further includes an intracorporeal reference,a juxtaposition between the radiopaque marker and the intracorporealreference being extracorporeally fluoroscopically observable.

In an application, the intracorporeal reference includes a scaleincluding a plurality of radiopaque markers.

In an application, the plurality of radiopaque markers includes a firstplurality of radiopaque markers, and the at least one radiopaque markerincludes a second plurality of radiopaque markers.

In an application, the spring is configured to provide distinctindication that is observable using fluoroscopy, when the spring isexperiencing a force that is within a margin force from a target force.

In an application, the spring is configured to provide the distinctindication when the spring experiences a force that is above 300 gforce.

In an application, the spring is configured to provide the distinctindication when the spring experiences a force that is above 400 gforce.

In an application, the spring is configured to provide the distinctindication when the spring experiences a force that is about 500 gforce.

In an application, the spring is coupled to the prosthetic valve, and isintracorporeally lockable to the tether subsequently to anchoring of thetissue anchor to the ventricular muscle tissue.

In an application, the spring is slidable along at least part of thetether, and is intracorporeally couplable to the tether by inhibitingthe sliding.

In an application, the prosthetic valve includes a generally cylindricalvalve body having an upstream end, and the spring includes anelastically-deformable appendage that protrudes laterally from the valvebody.

In an application:

the prosthetic valve includes a generally cylindrical valve body havingan upstream end, a downstream end, and a longitudinal lumentherebetween, and

the spring (1) includes a compression spring having a longitudinal axis,and (2) is disposed laterally from, the valve body such that thelongitudinal axis of the spring is generally parallel with thelongitudinal lumen.

In an application, the prosthetic valve includes:

a generally cylindrical valve body having an upstream end, a downstreamend, and a longitudinal lumen therebetween; and

one or more tissue-engaging legs, protruding laterally outward from thevalve body, and configured to be placed against a ventricular surface ofthe native valve.

In an application, the prosthetic valve is couplable to the upstreamsupport intracorporeally by being expanded within an opening defined bythe upstream support while the upstream support is disposed against theupstream surface.

In an application, the apparatus is configured such that the coupling ofthe prosthetic valve to the upstream support couples the tether to theprosthetic valve.

In an application, the apparatus is configured to sandwich a portion ofthe native valve between the tissue-engaging legs and the upstreamsupport by providing a space having a height between the tissue-engaginglegs and the upstream support.

In an application, the apparatus is configured to facilitate alteringthe height without altering a force on the spring.

In an application, the apparatus is configured such that altering theheight automatically alters a force on the spring.

In an application, the apparatus is configured to facilitate alteringthe height by moving the valve body through the opening defined by theupstream support.

There is further provided, in accordance with an application of thepresent invention, apparatus for use with a native heart valve of asubject, the apparatus including:

a valve body:

-   -   having an upstream end, a downstream end, and a longitudinal        axis therebetween,    -   including a lateral wall that circumscribes the longitudinal        axis and defines a longitudinal lumen, and    -   including a valve member disposed within the lumen;

an upstream support having an inner perimeter couplable to the valvebody at a first longitudinal position of the valve body, the upstreamsupport being configured to extend radially outward from the valve bodyand the inner perimeter; and

a flexible sheet defining a first aperture, a second aperture and alateral wall therebetween, a first portion of the sheet that defines thefirst aperture being circumferentially attached to the upstream supportportion at a radius that is greater than a radius of the innerperimeter, and a second portion of the sheet that defines the secondaperture being circumferentially attached to the valve body at a secondlongitudinal position of the valve body, such that a pocket region isdefined between the sheet and at least the first longitudinal position.

In an application, the second longitudinal position is closer to thedownstream end of the valve body than is the first longitudinalposition.

In an application, the first aperture is larger than the secondaperture.

In an application, the sheet is attached to the upstream support at anouter perimeter of the upstream support.

In an application, the sheet assumes a frustoconical shape.

In an application, the sheet assumes a funnel shape.

In an application, the apparatus is provided with the inner perimeter ofthe upstream support pre-coupled to the valve body at the firstlongitudinal position of the valve body.

In an application, the apparatus is configured such that the innerperimeter of the upstream support is intracorporeally couplable to thevalve body at the first longitudinal position of the valve body.

There is further provided, in accordance with an application of thepresent invention, apparatus for use with a native heart valve disposedbetween an atrium and a ventricle of a heart of a subject, the apparatusincluding:

an annular upstream support defining an opening therethrough, andconfigured to be placed against an upstream surface of the native heartvalve;

a tubular valve body having an upstream end, a downstream end and alumen therebetween, the lumen having a first diameter, and the valvebody being separated from the upstream element by a gap between theupstream end of the valve body and the upstream element;

one or more tissue-engaging elements that protrude radially outward fromthe valve body so as to define a second diameter that is greater thanthe first diameter; and

a flexible sheet shaped to define a conduit, a downstream portion of thesheet being coupled to the valve body, an upstream portion of the sheetbeing coupled to the upstream element, and the sheet spanning the gap.

In an application, the apparatus further includes at least one tether, afirst portion of the tether being coupled to the valve body and a secondportion of the tether being coupled to the upstream support, such thattensioning of at least a portion of the tether reduces the gap.

In an application, the apparatus is configured such that tensioning ofat least the portion of the tether rumples the sheet.

There is further provided, in accordance with an application of thepresent invention, apparatus for use with a native heart valve disposedbetween an atrium and a ventricle of a heart of a subject, the apparatusincluding:

an annular upstream element defining an opening therethrough, andconfigured to be placed against an upstream surface of the native heartvalve;

a flexible sheet, shaped to define a conduit, and coupled to theupstream element such that the conduit is in fluid communication withthe opening; and

a valve body, coupled to the flexible sheet such that the conduitprovides fluid communication between the prosthetic valve and theupstream element.

In an application, the valve body includes:

a generally cylindrical frame shaped to define a lumen therethrough, anda valve member coupled to the frame and disposed within the lumen.

In an application, the frame is separated from the upstream element by agap, and the conduit spans the gap.

There is further provided, in accordance with an application of thepresent invention, apparatus, for use with a guide member that extendsinto a subject, the apparatus including:

a delivery tool, including a housing, the housing:

-   -   being transluminally advanceable into the subject,    -   shaped to define an orifice at an end of the housing, and    -   having a lateral wall shaped to define a slit that is continuous        with the orifice; an implant:    -   configured to be housed by the housing, and    -   including an eyelet that (1) is slidable over the guide member,        and (2) when the implant is housed by the housing, extends        through the slit and radially beyond the lateral wall such that        the eyelet facilitates transluminal sliding of the implant and        the housing along the guide member and into the subject,        the apparatus being configured such that, while (1) the implant        remains within the subject, and (2) the guide member remains        disposed through the eyelet, (1) the implant is removable from        the housing via the orifice, and (2) the housing is removable        from the subject.

In an application, the implant is configured to be implanted by beingintracorporeally locked to the guide member.

In an application, the implant has a compressed state and an expandedstate, is configured to be housed by the housing while in the compressedstate, and is configured to automatically expand toward the expandedstate when removed from the housing.

There is further provided, in accordance with an application of thepresent invention, a method for use with a native valve of a heart of asubject, the method including:

transluminally anchoring a tissue anchor to ventricular tissue of asubject using an anchor-manipulation tool, the tissue anchor beingcoupled to a first portion of a tether;

transluminally delivering an annular upstream support and a prostheticvalve to the heart, the prosthetic valve including (1) a valve bodyshaped to define a lumen therethrough, and (2) one or moretissue-engaging legs configured to protrude laterally outward from thevalve body;

pressing the tissue-engaging legs in an upstream direction against aventricular surface of the native valve by applying a force to theprosthetic valve while measuring the force;

applying, to the tether, a tension that changes a shape of a springcoupled to the tether, while observing the shape of the spring usingimaging; and

at least in part responsively to the observed shape of the spring,facilitating holding of the upstream support against an upstream surfaceof the native valve by locking a second portion of the tether to atleast one component selected from the group consisting of: theprosthetic valve and the upstream support.

In an application, measuring the force includes measuring the forceusing an extracorporeal force meter.

In an application, measuring the force includes observing a shape of thetissue-engaging legs using imaging.

In an application, applying the tension includes applying the tensionwhile applying the force.

In an application, locking the second portion to the selected componentincludes locking the second portion to the prosthetic valve.

In an application, locking the second portion to the selected componentincludes locking the second portion to the upstream support.

In an application, locking the second portion includes locking thesecond portion when the observed shape indicates that the spring isexperiencing between 400 g force and 600 g force.

In an application, locking the second portion includes locking thesecond portion subsequently to applying the tension, and applying theforce includes applying the force subsequently to locking the secondportion.

In an application:

anchoring the tissue anchor coupled to the tether includes anchoring afirst tissue anchor coupled to a first tether, and applying the tensionincludes applying a first tension that changes a shape of a first springcoupled to the first tether,

the method further includes:

-   -   anchoring a second tissue anchor to the ventricular tissue, the        second tissue anchor being coupled to a first portion of a        second tether; and    -   applying, to the second tether, a second tension that changes a        shape of a second spring coupled to the second tether, while        observing the shape of the second spring using imaging, and

facilitating holding of the prosthetic valve against the upstreamsurface includes, at least in part responsively to the observed shape ofthe second spring, facilitating holding of the prosthetic valve againstthe upstream surface by locking a second portion of the second tether tothe selected at least one component.

In an application, facilitating holding includes locking the secondportion of the first tether and the second portion of the second tetherto the selected at least one component, at least in part responsively toa ratio between tension in the first tether and tension in the secondtether, the ratio being derived from the observed shape of the firstspring and the observed shape of the second spring.

In an application, locking includes locking the second portion to the atleast one component at least in part responsively to the observed shape.

In an application, locking includes locking the second portion to the atleast one component at least in part responsively to the measured force.

In an application, applying the force includes moving the valve body inan upstream direction through an opening defined by the upstreamsupport, and the method further includes coupling the prosthetic valveto the upstream support by expanding the valve body within the opening.

In an application, coupling the prosthetic valve to the upstream supportincludes coupling the prosthetic valve to the upstream support at leastin part responsively to the measured force.

There is further provided, in accordance with an application of thepresent invention, a method, including:

transluminally advancing a plurality of tissue anchors, coupled to arespective plurality of springs, into a body of a subject;

anchoring the plurality of tissue anchors to tissue of the subject;

tensioning at least one of the springs;

using imaging, while the tension is applied to the at least one spring,observing a state of the at least one spring; and

at least in part responsively to the observed state of at least onespring, adjusting a tension on at least one of the springs.

There is further provided, in accordance with an application of thepresent invention, a method, for use with a native valve of a heart of asubject, the method including:

applying a first tension to a tether that couples (a) a tissue anchoranchored to ventricular tissue of a subject, to (b) a prosthetic valvebody, the tether having a length between the tissue anchor and the valvebody;

by applying an atrially-directed force to the prosthetic valve body,pressing, against tissue of the native valve, a tissue-engaging elementthat protrudes radially from the valve body

transluminally advancing a prosthetic valve body to a native valve ofthe subject;

while applying the atrially-directed force, measuring:

-   -   a pressing force of the tissue-engaging element against the        tissue of the native valve, and    -   a second tension on the tether, the second tension differing        from the first tension at least in part due to the        atrially-directed force; and

at least in part responsively to the measured pressing force and themeasured second tension, performing an action selected from the groupconsisting of: adjusting the length of the tether between the tissueanchor and the valve body, and locking the valve body to the tether.

There is further provided, in accordance with an application of thepresent invention, a method for use with a native valve of a heart of asubject, the method including:

transluminally delivering a tissue anchor to a ventricle of the heart,and anchoring the tissue anchor to ventricular muscle tissue of thesubject;

transluminally delivering an upstream support to an atrium of the heart,and placing the upstream support against an upstream surface of anannulus of the native valve; and

changing a shape of the upstream support by tensioning a tether coupledto upstream support and to the tissue anchor; and

extracorporeally fluoroscopically observing the shape change of theupstream support.

In an application, tensioning the tether coupled to the upstream supportincludes tensioning a tether that is coupled to a valve body coupled tothe upstream support.

In an application, before the tensioning, the upstream support isgenerally flat annular, and changing the shape includes making thesupport assume a frustoconical shape.

In an application, before the tensioning, the upstream support isfrustoconical, and changing the shape includes changing a slant of thefrustoconical shape.

There is further provided, in accordance with an application of thepresent invention, apparatus for use with a valve of a heart of asubject, the apparatus including:

a transluminally-deliverable tissue anchor;

a tether, a first end thereof coupled to the tissue anchor; and

a delivery tool, including:

-   -   a steerable catheter having a longitudinal axis, and being        transluminally deliverable to the valve, and    -   an obstructing element:        -   disposed at a longitudinal site of the catheter,        -   configured to extend laterally outward from the catheter,            and        -   dimensioned, when extending laterally outward from the            catheter, to inhibit movement of at least the longitudinal            site through the valve by abutting tissue of the valve, and    -   an anchor manipulator:        -   reversibly couplable to the tissue anchor,        -   slidable through the catheter, and        -   configured to drive the anchor into ventricular tissue of            the heart of the subject.

In an application, the anchor manipulator is slidably coupled to thecatheter such that a distal end of the anchor manipulator is slidabledistally no more than a pre-determined distance from the longitudinalsite.

In an application, the apparatus further includes an implant,intracorporeally lockable to the tether.

In an application, the apparatus further includes a guide member,reversibly couplable to the tether, and the implant is intracorporeallyslidable along the guide member toward the tether and the implant.

In an application, the tether has exactly one locking site at which theimplant is lockable to the tether.

In an application, the exactly one locking site is disposed at apre-determined distance from the anchor that is pre-determined at leastin part dependently on a distance between the longitudinal site and adistal end of the catheter.

There is further provided, in accordance with an application of thepresent invention, a method, including:

transluminally anchoring a tissue anchor to tissue of a subject using ananchor-manipulation tool;

subsequently applying to the anchor a pulling force having a givenmagnitude;

using imaging, observing a movement of the tissue anchor in response tothe pulling force; and

at least in part responsively to the observed movement, performing anaction selected from the group consisting of: de-anchoring the tissueanchor from the tissue, and decoupling the anchor-manipulation tool fromthe tissue anchor.

There is further provided, in accordance with an application of thepresent invention, apparatus, for implantation at a native valve of aheart of a subject, the native valve being disposed between an atriumand a ventricle of the heart, the apparatus including:

a tubular valve body:

-   -   having an upstream portion, configured to be disposed in the        atrium of the heart of the subject,    -   having a downstream portion, configured to be disposed in the        ventricle of the subject,    -   having an elastic portion, disposed between the upstream portion        and the downstream portion, and elastically coupling the        upstream portion to the downstream portion, and    -   shaped to define a continuous lumen through the upstream        portion, the elastic portion, and the downstream portion; and

at least one valve member, disposed in the lumen of the valve body, andconfigured to facilitate flow of blood of the subject from the upstreamportion of the valve body to the downstream portion of the valve body,and to inhibit flow of the blood from the downstream portion of thevalve body to the upstream portion of the valve body.

In an application, the at least one valve member is coupled to thedownstream portion of the valve body.

In an application, the native valve includes a plurality of nativeleaflets, and the downstream portion of the valve body is configured tobe coupled to the native leaflets.

In an application, the apparatus further includes a plurality of clips,configured to facilitate the coupling of the downstream portion of thevalve body to the native leaflets.

In an application, each clip:

includes at least two clip arms, articulatably coupled to each other,and

is reversibly closeable.

In an application, the clips are coupled to the downstream portion ofthe valve body, and the downstream portion of the valve body isconfigured to be coupled to the native leaflets by the clips beingcoupled to the native leaflets.

In an application, each clip of the plurality of clips is articulatablycoupled to the downstream portion of the valve body.

In an application, the native valve includes an annulus having anupstream surface, and the apparatus further includes a prosthetic valvesupport:

including (1) an upstream support portion, configured to be placedagainst the upstream surface of the annulus of the native valve, and (2)the plurality of clips, coupled to the upstream support portion,

shaped to define an opening therethrough that is configured to receivethe prosthetic valve,

and the clips are configured to facilitate the coupling of thedownstream portion of the valve body to the native leaflets by couplingthe prosthetic valve support to the native leaflets.

There is further provided, in accordance with an application of thepresent invention, apparatus for use with a native valve of a heart of asubject, the native valve having a plurality of leaflets that meet at aplurality of commissures, the apparatus including:

at least one tissue anchor, configured to be anchored to a first sitewithin a ventricle of the heart of the subject;

at least one longitudinal member, coupled at a distal end thereof to arespective one of the at least one tissue anchors;

an upstream support, including an upstream support portion configured tobe slidable over the longitudinal member and placed against an upstreamsurface of the native valve; and

at least one locking member, configured to be slidable over a respectiveone of the at least one longitudinal members, and to be lockable to therespective longitudinal member such that a portion of the respectivelongitudinal member that is disposed between the respective anchor andthe upstream support portion is longer than 1 cm.

In an application, the longitudinal member is flexible.

In an application, the longitudinal member includes a suture.

There is further provided, in accordance with an application of thepresent invention, a method for use with a native valve of a heart of asubject, the native valve having a plurality of leaflets that meet at afirst commissure and at a second commissure, the method including:

anchoring a first tissue anchor to a first site within a ventricle ofthe heart of the subject, the first tissue anchor being coupled to adistal end of a first longitudinal member;

anchoring a second tissue anchor to a second site within the ventricleof the heart of the subject, the second tissue anchor being coupled to adistal end of a second longitudinal member;

subsequently, placing at least an upstream support portion of aprosthetic valve support against an upstream surface of the nativevalve, the valve being disposed between the ventricle and an atrium ofthe heart of the subject; and

securing the upstream support portion against the upstream surface ofthe valve by:

-   -   coupling the upstream support portion to the first longitudinal        member such that at least part of a portion of the first        longitudinal member that is disposed between the upstream        support portion and the first tissue anchor, is disposed between        the first and second leaflets at the first commissure, and    -   coupling the upstream support portion to the second longitudinal        member such that at least part of a portion of the second        longitudinal member that is disposed between the upstream        support portion and the first tissue anchor, is disposed between        the first and second leaflets at the second commissure.

In an application, anchoring, placing, and securing include anchoring,securing, and placing without the use of cardiopulmonary bypass.

In an application, anchoring to the first site and anchoring to thesecond site include anchoring to myocardium.

In an application, placing the upstream support portion against theupstream surface includes sliding the upstream support portion over atleast part of the first longitudinal member.

In an application, coupling the upstream support portion to the firstlongitudinal member and to the second longitudinal member includescoupling the upstream support portion to the first longitudinal memberin the atrium of the heart of the subject, and coupling the upstreamsupport portion to the second longitudinal member includes coupling theupstream support portion to the second longitudinal member in the atriumof the heart of the subject.

In an application, the leaflets move in response to beating of the heartof the subject, and securing the upstream support portion includessecuring the upstream support portion without eliminating the movementof the native leaflets.

In an application, coupling the upstream support portion to the firstlongitudinal member includes coupling the upstream support portion tothe first longitudinal member such that a length of the portion of thefirst longitudinal member is greater than 1 cm.

In an application, the method further includes:

transluminally advancing at least the first tissue anchor to the firstsite while the respective longitudinal member coupled thereto isdisposed within a respective tubular member; and

subsequently to anchoring the at least first tissue anchor, and beforecoupling the upstream support portion to the respective longitudinalmember, sliding the at least first tubular member off of at least partof the respective longitudinal member.

In an application, sliding the at least first tubular member includessliding at least part of the at least first tubular member through achannel defined by a locking member, and coupling the upstream supportportion to the respective longitudinal member includes locking thelocking member to the respective longitudinal member by narrowing atleast a portion of the channel

In an application:

advancing the at least first tissue anchor includes advancing the atleast first tissue anchor while (1) the respective longitudinal memberis reversibly coupled to a portion of a wire, and (2) the respectivetubular member inhibits the portion of the wire from decoupling from theportion of the wire, and

the method further includes facilitating decoupling of the wire from therespective longitudinal member by sliding the at least first tubularmember off of the portion of the wire.

In an application:

advancing the at least first tissue anchor includes advancing the atleast first tissue anchor while (1) the respective longitudinal memberis shaped to define a loop, and is coupled to the portion of the wire bythe portion of the wire being threaded through the loop, and (2) therespective tubular member inhibits the portion of the wire fromunthreading from the loop, and

facilitating decoupling of the wire from the respective longitudinalmember includes facilitating unthreading of the wire from the loop bysliding the at least first tubular member off of the portion of thewire.

In an application, sliding the at least first tubular member off of theportion of the wire includes sliding the at least first tubular memberoff of the portion of the wire by applying less than 500 g of pullingforce to the at least first tubular member.

In an application, applying less than 500 g of pulling force to the atleast first tubular member includes applying less than 300 g of pullingforce to the at least first tubular member.

In an application, the method further includes, subsequently to securingthe upstream support portion, coupling a prosthetic valve to theprosthetic valve support.

In an application, the upstream support portion has an inner edge thatdefines an opening through the upstream support portion, and couplingthe prosthetic valve to the prosthetic valve support includes placing atleast a portion of the prosthetic valve within the opening, andexpanding at least the portion of the prosthetic valve such that atleast the portion of the prosthetic valve applies a radially-expansiveforce against the inner edge of the upstream support portion.

In an application, the prosthetic valve includes one or moretissue-engaging elements, each of the one or more tissue-engagingelements including at least two arms, and the method further includes,subsequent to securing the upstream support portion, coupling theprosthetic valve to at least one of the leaflets by sandwiching the atleast one of the leaflets between the at least clip arms of the one ormore tissue-engaging elements.

In an application, coupling the prosthetic valve to the at least one ofthe leaflets includes coupling the prosthetic valve to the at least oneof the leaflets before coupling the prosthetic valve to the prostheticvalve support.

In an application:

the prosthetic valve includes a valve body, having an outer surface,

the at least two arms include a first arm and a second arm, the firstarm being longer than the second arm, and

the method further includes:

-   -   delivering, within a delivery tube, the prosthetic valve in a        delivery configuration thereof, in which the first arm and the        second arm are constrained against the outer surface of the        valve body;    -   facilitating deflection of the first arm away from the outer        surface of the prosthetic valve, by advancing a first portion of        the prosthetic valve out of the delivery tube such that the        first arm automatically deflects away from the outer surface of        the prosthetic valve; and    -   facilitating deflection of the second arm away from the outer        surface of the prosthetic valve, by advancing a second portion        of the prosthetic valve out of the delivery tube such that the        second arm automatically deflects away from the outer surface of        the prosthetic valve.

In an application:

facilitating deflection of the first arm includes facilitatingdeflection of the first arm a first angle from the outer surface of theprosthetic valve, and

the method further includes facilitating deflection of the first armaway from the outer surface of the prosthetic valve a second angle thatis greater than the first angle, by applying a force to the first armusing the delivery tube:

-   -   subsequently to facilitating deflection of the first arm the        first angle, and    -   prior to facilitating deflection of the second arm.

In an application, applying the force to the first arm using thedelivery tube includes pushing on the first arm by sliding the deliverytube over at least part of the prosthetic valve.

There is further provided, in accordance with an application of thepresent invention, apparatus for use with a body of a subject, theapparatus including:

at least a first implantable member;

a first longitudinal member, coupled at a distal end thereof to thefirst implantable member;

a second longitudinal member, at least a portion of the secondlongitudinal member being reversibly couplable to the first longitudinalmember; and

a tubular member:

-   -   slidable over the first and second longitudinal members,    -   shaped to define a lumen therethrough, and    -   configured, when the portion of the second longitudinal member        is (1) coupled to the first longitudinal member, and (2)        disposed within the lumen of the tubular member, to inhibit        decoupling of the portion of the second longitudinal member from        the first longitudinal member.

In an application, the portion of the second longitudinal member isconfigured, when (1) the portion of the second longitudinal member iscoupled to the first longitudinal member, and (2) the portion of thesecond longitudinal member is disposed outside of the lumen of thetubular member, to be decouplable from the first longitudinal member bythe second longitudinal member being pulled away from the firstlongitudinal member.

In an application, at least one longitudinal member selected from thegroup consisting of: the first longitudinal member and the secondlongitudinal member, is flexible.

In an application, the tubular member is more rigid than the firstlongitudinal member.

In an application, the tubular member fits snugly over at least theportion of the second longitudinal member.

In an application, the first implantable member includes a tissueanchor, configured to be anchored to a tissue of the subject.

In an application, the apparatus further includes a second implantablemember, slidable over the tubular member, and couplable to the firstlongitudinal member while the portion of the second longitudinal memberis coupled to the first longitudinal member.

In an application, the portion of the second longitudinal member isreversibly couplable to the first longitudinal member at a first site ofthe first longitudinal member, and the second implantable member iscouplable to the first longitudinal member at a second site of the firstlongitudinal member that is distal to the first site of the longitudinalmember.

In an application, the apparatus further includes a locking memberhaving an unlocked state and a locked state, and configured to be slidover the tubular member in the unlocked state and to be locked to thefirst longitudinal member by being transitioned to the locked state.

In an application, the locking member is configured to facilitatecoupling of the second implantable member to the first longitudinalmember.

In an application, the locking member is configured to be coupled to thefirst longitudinal member at least 1 cm away from the first implantablemember.

There is further provided, in accordance with an application of thepresent invention, apparatus for use at a native valve of a heart of asubject, the apparatus including:

a tissue anchor, configured to be transluminally, transcatheterallyadvanced to a ventricle of the heart of the subject, and to be coupledto tissue of the ventricle;

a longitudinal member, coupled at a distal end thereof to the tissueanchor;

a wire, a portion of the wire being reversibly couplable to thelongitudinal member;

a tubular member:

-   -   slidable over the longitudinal member and the wire,    -   shaped to define a lumen therethrough, and

configured, when the portion of the wire is (1) coupled to thelongitudinal member, and (2) disposed within the lumen of the tubularmember, to inhibit decoupling of the portion of the wire from thelongitudinal member;

a prosthetic valve support including an upstream support portionslidable over the tubular member, and to be placed against an upstreamsurface of an annulus of the native valve by sliding over the tubularmember; and

a locking member, slidable over the tubular element and lockable to thelongitudinal member.

In an application, the locking member is configured to be locked to thelongitudinal member at a site of the longitudinal member that is distalto a site of the longitudinal member to which the portion of the wire isreversibly couplable.

In an application, the tubular member is configured to be slid out ofthe locking member before the locking member is locked to thelongitudinal member.

In an application, the apparatus further includes a control rod,slidable over the tubular member, the locking member being reversiblycoupled to a control rod, the control rod being configured to restrainthe locking member in an unlocked configuration thereof, and tofacilitate locking of the locking member by ceasing to restrain thelocking member in the unlocked configuration.

In an application, the control rod is configured to decouple from thelocking member when the control rod ceases to restrain the lockingmember in the unlocked configuration thereof.

In an application, the control rod is configured to cease to restrainthe locking member in the unlocked configuration thereof by the controlrod being rotated with respect to the locking member.

In an application:

the prosthetic valve support is shaped to define a hole through whichthe tubular member is slidable,

at least while the control rod is coupled to the locking member, thecontrol rod is not slidable through the hole defined by the prostheticvalve support, and

the control rod is configured to facilitate the sliding of theprosthetic valve support over the tubular member by pushing theprosthetic valve support over the tubular member.

The present invention will be more fully understood from the followingdetailed description of applications thereof, taken together with thedrawings, in which:

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1A-F are schematic illustrations of a system for implanting aprosthetic valve support and a prosthetic valve at a native valve of aheart of a subject, in accordance with some applications of theinvention;

FIG. 2 is a schematic illustration of the prosthetic valve beingretrieved into a delivery tube, in accordance with some applications ofthe invention;

FIGS. 3A-C are schematic illustrations of the introduction of guidemembers through the prosthetic valve support and a delivery tube, inaccordance with some applications of the invention;

FIGS. 4A-C are schematic illustrations of a locking member, and controlthereof, in accordance with some applications of the invention;

FIG. 5 is a schematic illustration of steps in the delivery andanchoring of tissue anchors, in accordance with some applications of theinvention;

FIG. 6 is a schematic illustration of a system for use with a prostheticvalve support, in accordance with some applications of the invention;

FIGS. 7A-C are schematic illustrations of a system for facilitatingtransluminal delivery of a prosthetic valve assembly, in accordance withsome applications of the invention;

FIGS. 8A-H are schematic illustrations of a technique for use with thesystem of FIGS. 7A-C, to transluminally implant a prosthetic valveassembly, in accordance with some applications of the invention;

FIGS. 9A-B, 10A-B, 11A-B, 12A-B, 13A-B, and 14A-B are schematicillustrations of prosthetic valve assemblies, in accordance with someapplications of the invention;

FIGS. 15A-C are schematic illustrations of a tool for facilitatingapplication of force between a prosthetic valve assembly and tethers, inaccordance with some applications of the invention;

FIG. 16 is a schematic illustration of a system comprising a prostheticvalve assembly and one or more springs, via which the prosthetic valveassembly is elastically coupled to one or more tissue anchors, inaccordance with some applications of the invention;

FIG. 17 is a schematic illustration of a system comprising a prostheticvalve assembly and one or more springs, via which the prosthetic valveassembly is elastically coupled to one or more tissue anchors, inaccordance with some applications of the invention;

FIGS. 18A-B are schematic illustrations of springs coupled to respectivetethers so as to elastically couple a tissue anchor to a prostheticvalve assembly, in accordance with some applications of the invention;

FIGS. 19A-B are schematic illustrations of a system for facilitatingdelivery of a prosthetic valve body, in accordance with someapplications of the invention;

FIG. 20 is a schematic illustration showing examples in which forcemeasurements described herein may be combined to facilitate implantationof a prosthetic valve, in accordance with some applications of theinvention;

FIGS. 21A-B are schematic illustrations of a prosthetic valve assembly,in accordance with some applications of the invention;

FIGS. 22A-B are schematic illustrations of a prosthetic valve assemblycomprising a prosthetic valve having a tubular valve body that comprisesan upstream portion, a downstream portion, and an elastic portiondisposed between the upstream portion and the downstream portion, inaccordance with some applications of the invention; and

FIGS. 23-24 are schematic illustrations of systems for facilitatinganchoring of a tissue anchor in the heart of a subject, in accordancewith some applications of the invention.

DETAILED DESCRIPTION OF EMBODIMENTS

Reference is made to FIGS. 1A-F, which are schematic illustrations of asystem 40 for implanting an upstream prosthetic valve support 42 and aprosthetic valve 44 at a native valve 10 of a heart 4 of a subject, inaccordance with some applications of the invention. Typically,applications of the invention are for use with the mitral valve of thesubject (that is, native valve 10 comprises the mitral valve of thesubject), but it is to be noted that applications of the invention maybe used at other heart valves of the subject, such as the tricuspidvalve, the aortic valve, or the pulmonary valve, mutatis mutandis.

Reference is now made to FIGS. 1A-B. A sheath 46 is advancedtransluminally (e.g., transfemorally) to right atrium 12 of the heart,and is typically advanced through the fossa ovalis into left atrium 6 ofthe heart using standard transseptal techniques. For some applications,sheath 46 is steerable. For some such applications, sheath 46 issteerable in two axes. One or more (typically two) tissue anchors 48 areadvanced through sheath 46, between leaflets 14 of the native valve, andinto left ventricle 8 of the heart, and are there anchored to tissue(e.g., ventricular muscle tissue) of the heart. FIG. 1A shows a firsttissue anchor 48 a being anchored at a first ventricular site, and FIG.1B shows a second tissue anchor 48 b being anchored at a secondventricular site. Typically, anchors 48 are anchored to muscle of theheart, such as to the walls of ventricle 8 and/or to papillary muscles.Typically, and as shown, anchors 48 comprise helical anchors that areanchored by being rotated. However, other types of anchors may be used,such as barbed or harpoon-like anchors, e.g., that are anchored by beingpushed into the tissue.

State A of FIGS. 1A and 1B show a catheter 50 having been advancedthrough sheath 46 and into ventricle 8, and an anchor-delivery tube 52having been advanced through catheter 50 to the respective ventricularsite. Typically, and as shown, the distal end of delivery tube 52 isplaced against the tissue at the ventricular site. Typically, at least adistal portion of catheter 50 is steerable (e.g., independently ofsheath 46).

State B of FIGS. 1A and 1B each show a respective anchor 48 beinganchored to a respective ventricular site. Typically, anchor 48 isreversibly coupled to an anchor manipulator 54 (e.g., an anchor driver),which is slidable through at least part of tube 52, and which isconfigured to apply a force (e.g., a rotational force) to the anchor soas to anchor the anchor at the ventricular site. For some applications,anchor manipulator 54 and anchor 48 are advanced from outside thesubject to the ventricular site only once the distal end of tube 52 isdisposed against the ventricular site. For some applications, themanipulator and anchor are disposed within, and advanced with, tube 52.For some applications, anchor 48 is anchored by rotating anchormanipulator 54 and tube 52 together. For some applications, a separateanchor manipulator 54 is used to deliver and anchor each anchor 48(e.g., each anchor 48 may be provided pre-coupled to a respective anchormanipulator). For some applications, one anchor manipulator 54 may beused to deliver and anchor all (e.g., both) anchors 48 (e.g., eachanchor 48 may be configured to be sequentially coupled to the anchormanipulator outside the body of the subject by the operating physician).It is to be noted that typically anchor 48 is not exposed from tube 52other than when being anchored. It is hypothesized that for someapplications this reduces a likelihood of inadvertently engaging and/ordamaging tissue of the heart (e.g., chordae tendineae).

For some applications, subsequent to anchoring each tissue anchor 48 tothe tissue, a testing pulling force of known magnitude is applied to theanchor (e.g., by applying the pulling force to anchor manipulator 54),and movement of the tissue anchor in response to the pulling force isobserved using imaging (e.g., fluoroscopy). The observed movement may beused to confirm successful and/or stable anchoring (e.g., relativelylittle movement may indicate firm anchoring in firm tissue) or todetermine sub-optimal anchoring (e.g., relatively large movement mayindicate weak anchoring and/or anchoring in weak tissue). Thus, at leastin part responsively to the observed movement, the operating physicianmay decouple manipulator 54 from anchor 48, or may de-anchor the anchorfrom the tissue using the manipulator.

State C of FIGS. 1A and 1B show anchor manipulator 54 having beendecoupled from anchor 48, and the manipulator and tube 52 beingwithdrawn proximally into catheter 50. Each anchor 48 is providedpre-coupled to a guide member 56 (e.g., a first guide member 56 a, and asecond guide member 56 b), described in more detail hereinbelow (e.g.,with reference to FIGS. 1D and 4A-C). As manipulator 54 and tube 52 arewithdrawn, guide member 56 is exposed from tube 52.

Typically, and as shown in FIGS. 1A-B, the same catheter 50 is used todeliver both anchors 48. For such applications, and as shown in states Band C of FIG. 1B, when delivering second tissue anchor 48 b,anchor-delivery tube 52 fits alongside first guide member 56 a withincatheter 50. Alternatively, and as described hereinbelow with referenceto FIG. 5, a separate catheter is used for each anchor, in which casethe second catheter fits alongside first guide member 56 a within sheath46.

State D of FIGS. 1A and 1B show catheter 50 having been withdrawnproximally, into atrium 6. For some applications, catheter 50 iswithdrawn completely from the body of the subject. For someapplications, catheter 50 is used for delivery of components duringlater steps in the procedure. Guide members 56 extend from atrium 6,between leaflets 14, and to respective ventricular sites. Typically,guide members 56 do not eliminate functioning of leaflets 14 and/orvalve 10. For some applications, guide members 56 are configured toautomatically move toward respective commissures 16 (e.g., into thejoining corners at the commissures of leaflets 14). For someapplications, and as shown in FIG. 1C, prosthetic valve support 42(e.g., deployment thereof) pushes guide members 56 toward the respectivecommissures.

Reference is now made to FIG. 1C, which shows prosthetic valve supportbeing delivered to, and deployed at, native valve 10. Prosthetic valvesupport 42 is advanced through sheath 46 and into atrium 6. Typically,support 42 is delivered in a compressed configuration thereof, within ahousing, such as a delivery tube 80. For some applications, catheter 50is used to facilitate delivery of prosthetic valve support 42 anddelivery tube 80 (e.g., the support and delivery tube are advancedthrough catheter 50). For some applications, a different catheter isused to facilitate delivery of prosthetic valve support 42 and deliverytube 80. For some applications, prosthetic valve support 42 and deliverytube 80 are advanced directly through sheath 46.

Prosthetic valve support 42 comprises an annular upstream supportportion 43 which, in the delivery configuration of the prosthetic valvesupport, is generally cylindrical, and which, once the prosthetic valveis deployed and expands to an uncompressed configuration thereof, isgenerally annular. For some applications, upstream support portion 43 isgenerally frustoconical in the uncompressed configuration thereof.Typically, a distal end of upstream support portion 43 in thecompressed, cylindrical configuration, defines an inner perimeter of theupstream support portion in the uncompressed configuration, the innerperimeter defining an opening through the upstream support portion.

State A of FIG. 1C shows delivery tube 80, containing support 42, havingbeen delivered to atrium 6 over guide members 56, and support 42starting to be subsequently exposed from the delivery tube, andautomatically expanding. Upstream support portion 43 of prosthetic valvesupport 42 is shaped to define holes 82 through which guide members 56are slidable, thereby facilitating sliding of the prosthetic valvesupport over guide members 56. Typically, holes 82 are disposed oppositeeach other around the generally annular shape of upstream supportportion 43. For some applications, holes 82 are defined and/orreinforced by an eyelet 84 or pledget (visible in states B and C of FIG.1C). Guide members 56 extend proximally from delivery tube 80, e.g., viaholes in a proximal end of the delivery tube, such that the deliverytube, and prosthetic valve support 42, in the compressed state withinthe delivery tube, are slidable over the guide members, the guidemembers thereby facilitating delivery of the prosthetic valve supportwithin the delivery tube. Introduction of guide members 56 through theprosthetic valve support and delivery tube are described hereinbelowwith reference to FIGS. 3A-C.

State B of FIG. 1C shows prosthetic valve support 42 (e.g., upstreamsupport portion 43 thereof) having been completely deployed fromdelivery tube 80, and having automatically expanded to the uncompressedconfiguration thereof. Guide members 56 are typically pushed towardcommissures 16 by the expansion of support 42. For some applications,delivery tube 80 is subsequently removed from the body of the subject. Atubular control rod 86 is advanced over each guide member 56 towardprosthetic valve support 42, and is used to push prosthetic valvesupport 42 (e.g., upstream support portion 43 thereof) toward theannulus of valve 10. Control rods 86 have a cross-sectional diameterthat is larger than that of holes 82, and may thereby be used to pushagainst upstream support portion 43 without passing through the holes.

Typically, prosthetic valve support 42 (e.g., upstream support portion43 thereof) is provided with one or more (e.g., two) control filaments88 reversibly coupled thereto. Typically, filaments 88 are coupled toupstream support portion 43 at sites that are disposed opposite eachother around the generally annular shape of the upstream supportportion, and disposed evenly between holes 82. That is, in the expandedconfiguration of upstream support portion 43, a straight line betweenholes 82 is typically perpendicular to a straight line between the sitesat which filaments 88 are coupled to the upstream support portion. Itshould be noted that other numbers and arrangements of control filamentsmay also be used. Typically, each control filament 88 (1) comprises twoportions of a loop of filament that passes through upstream supportportion 43, loops around a downstream surface of the upstream supportportion (i.e., the surface that is placed in contact with the annulus ofthe native valve), and passes back through the upstream support portion,and (2) is decouplable from the upstream support portion by releasing afirst end of the filament and pulling a second end, thereby unthreadingand/or unlooping the control filament from the upstream support portion.

Control filaments 88 facilitate some manipulation of prosthetic valvesupport 42 following deployment from delivery tube 80. Typically,control rods 86 further facilitate such manipulation. State C of FIG. 1Cshows such manipulation of prosthetic valve support 42. For example, itmay be desirable to rotate the prosthetic valve support (e.g., toposition and/or orient the upstream support portion correctly withrespect to native valve 10, to control the order in which differentregions of upstream support portion 43 contact the native valve, and/orto uncoil control rods 86 and/or control filaments 88 from each other).

Reference is now made to FIG. 1D, which show steps in securingprosthetic valve support 42 against the upstream surface (e.g., theatrial surface) of native valve 10. Each guide member 56 typicallycomprises a tether (e.g., a longitudinal member 102), a pull-wire 104reversibly coupled to the longitudinal member, and a tubular member 100in which the longitudinal member and the pull-wire are disposed, thetubular member fitting snugly over the longitudinal member and thepull-wire so as to inhibit the pull-wire from becoming decoupled fromthe longitudinal member (e.g., to maintain a state of couplingtherebetween). Pull-wire 104 may or may not be metallic and may havevarious cross-sectional shapes (e.g., circular or rectangular).Typically, (1) longitudinal member 102 defines a loop (e.g., a closedloop) (2) a portion (e.g., a distal portion) of pull-wire 104 isthreaded through the loop defined by member 102 (e.g., is looped throughthe loop), and (3) the snug fitting of tubular member 100 over member102 and pull-wire 104 inhibits the portion of the pull-wire fromunthreading from the loop. It is to be noted that, although longitudinalmember 102 is shown as defining a loop that extends most (e.g., all) ofthe length of the longitudinal member, the loop may alternatively bedefined only at a proximal end of the longitudinal member.

For some applications, longitudinal member 102 and pull-wire 104 arecoupled via complementary screw threads. For example, longitudinalmember 102 may comprise, or be coupled to, a screw at a proximal endthereof, and pull-wire 104 may comprise, or be coupled to, a socket at adistal end thereof. For some applications, tubular member 100 is used todecouple (e.g., unscrew) pull-wire 104 from longitudinal member 102.

Tubular member 100 is typically more rigid than pull-wire 104 and/orlongitudinal member 102 (although it is still sufficiently flexible tobe transluminally delivered). This rigidity reduces a likelihood oftwisting, kinking, snagging, and/or other undesirable phenomenon orinteractions within the transluminal delivery system (e.g., withinsheath 46, catheter 50, and/or anchor-delivery tube 52). For someapplications tubular member 100 has a smoother surface than doespull-wire 104 or longitudinal member 102. For some applications, tubularmember 100, which is necessarily wider than pull-wire 104 and/orlongitudinal member 102, is also more visible using imaging techniquessuch as fluoroscopy. This advantageously allows an operating physicianto monitor the intracorporeal juxtaposition of the tubular members and,if necessary, to intervene, such as by revolving the tubular members(e.g., proximal ends thereof) around each other.

As described hereinabove, control rods 86 are used to push prostheticvalve support 42 toward the annulus of valve 10 by sliding the controlrod over a respective guide member 56 (i.e., over the tubular member 100of the respective guide member). Each control rod 86 is reversiblycoupled at a distal end thereof to a respective locking member 110 that,in an unlocked state thereof, is slidable over guide member 56. Thereby,the pushing of prosthetic valve support 42 is typically performed bypushing with both control rod 86 and locking member 110. State A of FIG.1D shows control rods 86 and respective locking members 110 having beenslid over respective tubular members 100 of respective guide members 56,such that prosthetic valve support 42 has been pushed against theannulus of valve 10. Typically, a counter force (e.g., a proximalpulling force) is applied to guide member 56 (e.g., to tubular member100, longitudinal member 102, and pull-wire 104) so as to facilitatesuch sliding.

State B of FIG. 1D shows tubular member 110 having been pulledproximally such that the distal end of the tubular member is disposedproximal to locking member 110, thereby exposing, from the tubularmember, progressive portions of longitudinal member 102, at least untilthe tubular member is not disposed between the longitudinal member andthe locking member (e.g., such that the locking member can directlycontact the longitudinal member). Typically, and as shown in state B ofFIG. 1D, tubular member 100 is pulled proximally such that the distalend thereof is disposed distal to the point at which longitudinal member102 and pull-wire 104 are coupled, thereby retaining the couplingtherebetween. While in this state, locking member 110 is locked tolongitudinal member 102 (e.g., to a portion of the longitudinal memberthat is disposed within a channel of the locking member). For someapplications, locking member 110 locks automatically in response towithdrawal of tubular member 100. For some applications, locking oflocking member 110 is independent of the withdrawal of the tubularmember. An embodiment of locking member 110 and control thereof isdescribed in more detail hereinbelow with respect to FIGS. 4A-C. It isto be noted that the scope of the invention also comprises the use ofother locking members such as crimp-based locking members, and alsocomprises other locking techniques such as tying.

Subsequently, and as shown in state C of FIG. 1D, tubular member 100 ispulled further proximally, such that the distal end of the tubularmember is disposed proximal to the point at which longitudinal member102 and pull-wire 104 are coupled, such that the pull-wire isdecouplable from the longitudinal member (e.g., unthreadable from theloop defined by the longitudinal member).

Typically, anchors 48 and longitudinal members 102 are configured towithstand a pulling force of at least 500 g, so as to withstand forceswithin the beating heart. The apparatus is typically configured suchthat a pulling force required to pull tubular member 100 proximally, isless than 500 g, such as less than 300 g. For some applications, such aconfiguration is achieved at least in part by reducing friction betweentubular member 100 and pull-wire 104, such as by thermally treating thepull-wire 104.

Subsequently, control rod 86, tubular member 100, and pull-wire 104 arepulled proximally, as shown in state D of FIG. 1D, thereby separatingthe control rod from locking member 110, and the pull-wire fromlongitudinal member 102. In order for control rod 86 to be pulledproximally, the control rod is decoupled from locking member 110 priorto said pulling. For some applications, the decoupling of control rod 86from locking member 110 is synchronous with the locking of the lockingmember (e.g., the same action locks the locking member and decouples thecontrol rod from the locking member, such as described hereinbelow withrespect to FIGS. 4A-C). For some applications, the decoupling of thecontrol rod from the locking member is independent of the locking of thelocking member.

It is to be noted that, as shown in FIG. 1D, for some applications,prosthetic valve support 42 (e.g., upstream support portion 43 thereof)is secured to the upstream surface of the annulus of native valve 10,only by anchors 48 that are anchored to tissue in ventricle 8 of thesubject. It is also to be noted that prosthetic valve support 42 iscoupled to longitudinal members 102 in atrium 6 of the subject.Typically, a distance L1 between each anchor 48 and the point ofupstream support portion 43 to which it is coupled (e.g., to arespective hole 82 and/or locking member 110) is greater than 0.5 cm,e.g., greater than 1 cm, such as greater than 2 cm. That is, the lengthof each longitudinal member 102 that is disposed between a respectiveanchor and upstream support portion 43 is typically greater than 0.5 cm,e.g., greater than 1 cm, such as greater than 2 cm. The length of eachlongitudinal member 102 that is disposed between the respective anchorand the upstream support portion is typically less than 10 cm (e.g.,less than 7 cm, such as less than 5 cm). Thereby, the ventricular sitesat which anchors 48 are anchored are typically more than 0.5 cm (e.g.,more than 1 cm, such as more than 2 cm) away from prosthetic valvesupport 42.

Reference is now made to FIG. 1E-F, which show steps in the delivery andimplantation of prosthetic valve 44 at native valve 10, facilitated byprosthetic valve support 42. Prosthetic valve 44 is advanced in adelivery configuration (e.g., in a compressed state), through sheath 46,typically within a delivery tube 120. Prosthetic valve 44 comprises astent-like valve body 122, typically comprising an expandable frame thattypically contains a shape-memory material such as nitinol. Valve body122 is shaped to define a lumen therethrough, and an inner surface ofthe valve body is typically lined with a covering, such as a fabric. Oneor more prosthetic valve members (not shown for clarity), such asprosthetic leaflets, are coupled to valve body 122 and disposed withinthe lumen thereof.

Prosthetic valve 44 further comprises one or more tissue-engagingelements 124. Typically, and as shown, valve 44 comprises twotissue-engaging elements 124 coupled to valve body 122 at sites that areon opposite sides of the circumference of the valve body. Eachtissue-engaging element 124 typically comprises two arms 126 (e.g., afirst clip arm 126 a and a second clip arm 126 b). For someapplications, and as shown, each arm 126 defines an arc that is coupledto valve body 122 at the base of the arc. For example, and as shown,each arm 126 may comprise a single arc of the same shape-memory materialas the frame of valve body 122. For some applications, one or both arms126 of each tissue-engaging element 124 may be covered in a covering,such as a fabric.

When valve 44 is in the compressed state thereof within delivery tube120, arms 126 are held against valve body 122 with a tip 127 of each armdisposed proximally to a site at which that arm is coupled to the valvebody. Each tissue-engaging element 124 is configured such that a tip 127a of arm 126 a is disposed distal to a tip 127 b of arm 126 b. Forexample, arm 126 a may be shorter than arm 126 b. Alternatively oradditionally, arm 126 a may be coupled to valve body 122 at a site thatis distal to a site at which arm 126 b is coupled to the valve body.

Prosthetic valve 44, within delivery tube 120, is advanced distallybetween leaflets 14 of native valve 10, and the prosthetic valve isprogressively advanced distally out of a distal end of the deliverytube, as shown in states A-B of FIG. 1E. It is to be noted that leaflets14 typically continue to function following implantation of prostheticvalve support 42, and may further continue to function while deliverytube 120 is disposed therebetween; the leaflets typically coapt aroundthe delivery tube. At a given degree of advancement of prosthetic valve44 out of delivery tube 120, first arm 126 a is deployed: tip 127 a ofeach first arm 126 a becomes exposed from the delivery tube and each arm126 a responsively deflects radially outward from valve body 122, towarda pre-set position (state B of FIG. 1E). Tip 127 b of each arm 126 bremains within delivery tube 120. Throughout the procedure, as distalportions of valve body 122 are progressively exposed from delivery tube120, they typically automatically expand toward an expanded state

Subsequently, and as shown in state D of FIG. 1E, prosthetic valve 44and delivery tube 120 are moved proximally (e.g., atrially) such thatarm 126 a of each tissue-engaging element 124 engages (e.g., captures) aleaflet 14 of native valve 10, e.g., such that a portion of each leafletis disposed between (1) each arm 126 a and (2) a respective second arm126 b and valve body 122. Optionally, subsequently to deployment offirst arm 126 a and prior to moving prosthetic valve 44 proximally, thefirst arm is deflected further from valve body 122 than its pre-setposition by applying a force to the first arm using the delivery tube.That is, an angle between the first arm and an outer surface of thevalve body is increased by applying the force to the first arm using thedelivery tube.

Typically, the force is applied by moving delivery tube 120 distallywith respect to the prosthetic valve (e.g., sliding the delivery tubeover at least part of the prosthetic valve), so as to push the arm, asshown in state C of FIG. 1E. It is hypothesized that such “opening” oftissue-engaging element 124 facilitates engagement of leaflets 14 (e.g.,engagement of a larger portion of leaflets 14). Subsequently, deliverytube 120 is returned proximally with respect to prosthetic valve 44,such that arm 126 a returns toward its pre-set position (state D of FIG.1E). For some applications, until at least the step shown in state D ofFIG. 1E, prosthetic valve 44 is retrievable into delivery tube 120 andremovable from the body of the subject, e.g., as described hereinbelowwith respect to FIG. 2.

Subsequently, delivery tube 120 is pulled further proximally withrespect to prosthetic valve 44, such that tip 127 b of second arm 126 bof each tissue-engaging element 124 becomes exposed from the deliverytube, and each arm 126 b responsively deflects radially outward fromvalve body 122, toward a pre-set position (state A of FIG. 1F), therebycoupling the tissue-engaging element to the leaflet by sandwiching aportion of a leaflet 14 between the first and second arms of eachtissue-engaging element. Second arm 126 b is typically configured, whencompletely unrestricted (e.g., in the absence of leaflet 14) to have apre-set position that is close to that of first arm 126 a, planar withthat of first arm 126 a, and/or further from valve body 122 than is arm126 a. For some applications, the difference in size and/or position ofthe arc of second arm 126 b to that of first arm 126 a facilitates thesecond arm to move into plane with, and/or beyond the plane of, thefirst arm.

Subsequently, prosthetic valve 44 is fully deployed by a proximal end ofthe prosthetic valve (e.g., valve body 122 thereof) being exposed fromdelivery tube 120 (e.g., by further withdrawing the delivery tubeproximally with respect to the prosthetic valve) (state C of FIG. 1F).The proximal end of prosthetic valve 44 responsively (e.g.,automatically) expands toward the expanded state thereof. Expansion ofthe prosthetic valve (e.g., of valve body 122 thereof) applies aradially-expansive force against prosthetic valve support 42 (e.g.,against an inner perimeter of upstream support portion 43 thereof),thereby coupling the prosthetic valve to the prosthetic valve support.Typically, prosthetic valve support 42 (e.g., the inner perimeter ofupstream support portion 43) restricts expansion of prosthetic valve 44,at least in part.

For some applications, and as shown in state B of FIG. 1F, subsequentlyto the coupling of tissue-engaging elements 124 to leaflets 14, andprior to coupling of prosthetic valve 44 to prosthetic valve support 42,the prosthetic valve is pulled proximally, e.g., so as to align aportion of valve body 122 with upstream support portion 43 and/or todraw leaflets 14 toward the upstream support portion.

It is to be noted that, for some applications, each tissue-engagingelement 124 comprises only one arm 126. For some such applications, theone arm 126 comprises and/or functions like first arm 126 a describedherein. For some such applications, the one arm 126 is configured tocouple to the leaflet by sandwiching a portion of the leaflet betweenthe one arm and valve body 122. For some such applications, the one arm126 is configured, when the prosthetic valve is pulled proximally asshown in state B of FIG. 1F, to sandwich a portion of the leafletbetween the one arm and prosthetic valve support 42 (e.g., upstreamsupport portion 43 thereof).

State D of FIG. 1F shows the implanted (e.g., final) state of prostheticvalve support 42 and prosthetic valve 44, following implantation thereofat native valve 10. For some applications, in this implanted state,prosthetic valve support 42 and prosthetic valve 44 are inhibited frommoving upstream (e.g., atrially) both by tissue anchors 48 and bytissue-engaging elements 124. That is, for some applications, resistanceto forces on support 42 and valve 44 from the functioning of the heartof the subject, is provided in part by anchors 48 and in part byelements 124. For some applications, in this implanted state, prostheticvalve support 42 and prosthetic valve 44 are inhibited from movingupstream mostly (e.g., solely) by tissue-engaging elements 124. That is,for some applications, resistance to forces on support 42 and valve 44from the functioning of the heart of the subject, is provided mostly(e.g., solely) by elements 124. For some such applications, anchors 48and longitudinal members 102 are thereby only required until prostheticvalve 44 has been implanted. It is to be noted that in both cases,prosthetic valve support 42 (e.g., upstream support portion 43 thereof)inhibits movement ventricularly of prosthetic valve 44, and of theprosthetic valve support itself.

Reference is again made to FIGS. 1D-F. For some applications, locking oflocking members 110 to longitudinal members 102 and/or decoupling ofpull-wires 104 from longitudinal members 102 (FIG. 1D) is not performeduntil after implantation of prosthetic valve 44 (FIGS. 1E-F). For suchapplications, it is thereby possible to adjust the length of the portionof longitudinal members 102 (e.g., tension on the longitudinal members)after implantation of prosthetic valve 44. For some applications, asimilar advantage is conferred by locking members being reversiblylockable, being locked before implantation of prosthetic valve 44, andsubsequently to implantation of the prosthetic valve, being unlocked toallow re-adjustment of longitudinal members 102.

Reference is again made to FIGS. 1A-F. For some applications, anatomicaldimensions of native valve 10 and/or surrounding tissues are determined(e.g., measured), and prosthetic valve support 42 and/or prostheticvalve 44 are selected accordingly (e.g., from a selection of prostheticvalve supports and/or prosthetic valves of different sizes). Forexample, an optimal lumen size (e.g., transverse cross-sectional area)for a prosthetic valve may be determined according to an area of thelumen defined by the annulus of the native valve of the subject.Responsively, a prosthetic valve having a lumen of that particular sizemay be selected. Similarly, a prosthetic valve support having an innerperimeter that defines an opening having a particular cross-sectionalarea may be selected, so as to restrict the expansion of a prostheticvalve to have a lumen of that particular size. Alternatively oradditionally, a prosthetic valve support having an outer perimeter of aparticular size may be selected according to determined dimensions ofthe annulus of the valve and/or walls of the atrium. It is to be notedthat selecting a size according to determined anatomical dimensions mayonly in some cases comprise selecting a size that matches the anatomicaldimensions. For example, an optimal size for the transversecross-sectional area of a prosthetic valve is typically less than 90% ofthe area defined by the annulus of the native valve, so as to allow theleaflets of the native valve to coapt around the prosthetic valve andfacilitate sealing.

Because prosthetic valve support 42 is typically implantable withouteliminating functioning of the native leaflets, for some applications,the prosthetic valve support is implantable without the use ofcardiopulmonary bypass. For some applications, prosthetic valve 44 isalso implantable without the use of cardiopulmonary bypass.

Reference is made to FIG. 2, which is a schematic illustration ofprosthetic valve 44 being retrieved into delivery tube 120, inaccordance with some applications of the invention. As describedhereinabove, for some applications, until at least the step shown instate D of FIG. 1E, prosthetic valve 44 is retrievable into deliverytube 120 and removable from the body of the subject. Delivery tube 120is moved distally with respect to prosthetic valve 44, in a mannersimilar to that used to push arms 126 a, described with reference toFIG. 1E (state C), but such that delivery tube 120 is slid over the siteat which arms 126 a are coupled to valve body 122, thereby pushing arms126 a to deflect distally. Prosthetic valve 44, including at least partof arms 126 a, is drawn into delivery tube 120 (e.g., by sliding theprosthetic valve distally and/or the delivery tube proximally), and istypically subsequently removed from the body of the subject.

Reference is made to FIGS. 3A-C, which are schematic illustrations ofthe introduction of guide members 56 through prosthetic valve support 42and delivery tube 80, in accordance with some applications of theinvention. As described hereinabove (e.g., with reference to FIG. 1C),prosthetic valve support 42 is slidable toward native valve 10, overguide members 56, including while the prosthetic valve support iscompressed within delivery tube 80. Following coupling of anchors 48 tothe ventricular sites, guide members 56 extend from the anchors tooutside of the body of the subject, and have respective free proximalends 57. Before introduction of support 42 within tube 80 into the bodyof the subject (e.g., into sheath 46), guide members 56 are threadedthrough holes 82 in upstream support portion 43 of prosthetic valvesupport 42, and through delivery tube 80, e.g., by the operatingphysician.

Typically, prosthetic valve support 42 is provided in the compressedstate thereof, within delivery tube 80, e.g., as a unit 140, coupled toa distal end of a controller 142 that is used to move the unittransluminally (e.g., within sheath 46). Unit 140 comprises (e.g., isprovided having) one or more introducer tubes 144, each introducer tubebeing shaped to define a lumen therethrough, and having an open distalend 143 and an open proximal end 145. Distal end 143 of each tube isdisposed outside a distal end of support 42 and/or tube 80, and proximalend 145 of each tube is disposed outside a proximal end of the supportand/or tube 80. Each introducer tube 144 passes (1) from the distal endthereof, (2) through a respective hole 82 in upstream support portion 43from the downstream surface of the support portion (which defines anouter surface of the support portion in the compressed state thereof) toan upstream surface of the support portion (which defines an innersurface of the support portion in the compressed state thereof), and (3)to the proximal end thereof.

As shown in FIG. 3A, free proximal end 57 of each guide member 56 isadvanced through a respective introducer tube 144, thereby threading theguide member through upstream support portion 43 of prosthetic valvesupport 42. Typically, and as shown in FIG. 3B, introducer tubes 144 aresubsequently removed, prior to introduction of unit 140 into the body ofthe subject. That is, introducer tubes 144 are typically temporary. FIG.3C shows upstream support portion 43 of prosthetic valve support 42having been partially exposed from delivery tube 80, in order toillustrate the resulting threading of guide members 56 through upstreamsupport portion 43.

Reference is made to FIGS. 4A-C, which are schematic illustrations oflocking member 110, and control thereof, in accordance with someapplications of the invention. As described hereinabove, locking member110 is slidable over guide member 56 (e.g., over tubular member 100thereof). As also described hereinabove, locking member 110 isconfigured to lock to longitudinal member 102.

FIG. 4A shows locking member 110 in the unlocked state thereof, in whichthe locking member typically defines a channel therethrough throughwhich tubular member 100 and longitudinal member 102, either within thetubular member or outside of the tubular member, are slidable. Thechannel of locking member 110 is defined by a generally tubular portion160 of the locking member. Tubular portion 160 defines one or more, suchas two, oblique slits 162 in the lateral walls thereof. Locking member110 comprises locking element, such as a locking bar 164, that isdisposed generally orthogonally to the channel of the locking member,and passes through the slits (e.g., through both slits) of the tubularmember. When locking bar 164 is slid distally and/or proximally, thelocking bar thereby moves across at least part of the channel defined bytubular portion 160. Locking member 110 further comprises a spring 166that is configured to push locking bar 164 in a given direction (e.g.,distally), thereby transitioning the locking member into the lockedconfiguration thereof (i.e., locking the locking member) (FIG. 4B).

Locking member 110 is typically controllable using a holding member 112that inhibits (e.g., prevents) the locking member from locking, such asby inhibiting movement of locking bar 164. As described hereinabove,each control rod 86, used to push prosthetic valve support 42 toward theannulus of valve 10, is reversibly coupled at a distal end thereof to arespective locking member 110, such that the pushing is typicallyperformed by pushing with control rod 86 and locking member 110. Forsome applications, and as shown in FIGS. 4A-C, holding member 112comprises and/or is defined by control rod 86. For such applications,control rod 86 defines one or more slits 168 in a lateral wall thereof(e.g., two slits 168 on opposite sides of the lateral wall of thecontrol rod). Typically, slits 168 are L-shaped, thereby providing (1) aholding region 170 that is generally orthogonal to the proximal-distal(e.g., longitudinal) axis of control rod 86, and (2) a release region172 that is generally parallel with the proximal-distal axis of thecontrol rod, and that is open to the distal end of the control rod.Locking bar 164 is configured such that ends thereof extend at leastinto (e.g., through) slits 168.

In the unlocked state in which locking member 110 is advanced over guidemember 56 toward upstream support portion 43 and the annulus of thenative valve, the ends of locking bar 164 are disposed in holding region170 of each slit 168, and the locking bar is thereby inhibited frommoving distally and locking the locking member (FIG. 4A). In order tolock the locking member, control rod 86 is rotated with respect tolocking member 110, such that the ends of locking bar 164 move intorelease region 172 of each slit 168. In this position, spring 166 isthereby able to move locking bar toward the distal end of release region172, thereby locking the locking member (FIG. 4B).

As described hereinabove, tubular member 100 is typically withdrawn fromlocking member 110 before the locking member is locked, and the lockingmember is locked to longitudinal member 102, e.g., by locking bar 164sandwiching longitudinal member 102 against the inner surface of thechannel of the locking member (e.g., effectively narrowing the channelat the site of the locking bar). Movement of the ends of locking bar 164into and through release region 172 also decouples control rod 86 fromthe locking member, allowing the control rod to be removed from the bodyof the subject (typically along with tubular member 100) (FIG. 4C). Forsome applications, longitudinal member 102 comprises suture. For someapplications, long member 102 comprises a polymer, such as polyester.For some applications, longitudinal member 102 comprises a metal. Forexample, the longitudinal member may comprise one or more wires, such asa plurality of wires twisted or braided into a cable. It is hypothesizedthat for some applications, a metallic composition reducescompressibility of longitudinal member 102 and/or facilitates locking oflocking member 110 to the longitudinal member.

It is to be noted that locking member 110 thereby (1) when unlocked,facilitates sliding therethrough of a relatively wide element, tubularmember 100, and (2) when locked, locks to a relatively narrow element,longitudinal member 102. To facilitate this, between the locked andunlocked states, locking bar 164 thereby moves a sufficient distanceacross the channel defined by locking member 110. That is, locking bar164 moves a larger distance than would be necessary to lock a similarlocking member that does not facilitate, in the unlocked state thereof,sliding therethrough of a tubular member that is wider than thelongitudinal element.

Reference is again made to FIGS. 1D and 4A-C. It is to be noted thatlocking member 110 is typically configured to lock to longitudinalmember 102 independently of (e.g., in the absence of) a complementaryelement, such as teeth, on the longitudinal member. For someapplications, locking member 110 is configured to be coupled to any partof longitudinal member 102.

Reference is made to FIG. 5, which is a schematic illustration of stepsin the delivery of tissue anchors 48 to ventricle 8, and anchoring ofthe anchors in the ventricle, in accordance with some applications ofthe invention. For some applications, the steps shown in FIG. 5 (and/orstates A-D thereof) can be used in place of the steps shown in FIG. 1B(and/or states A/D thereof), mutatis mutandis (e.g., after the stepsshown in FIG. 1A and/or before the steps shown in FIG. 1C). FIG. 1Bshows one delivery catheter 50 being used to deliver both anchors 48,and when delivering second tissue anchor 48 b, anchor-delivery tube 52fitting alongside first guide member 56 a within catheter 50. As statedhereinabove, for some applications, a separate catheter is used for eachanchor. FIG. 5 shows one such application.

Typically, first anchor 48 a is delivered and anchored as describedhereinabove with reference to FIG. 1A, wherein catheter 50 in FIG. 1Acomprises a first catheter 50 a. Subsequently, and as shown in FIG. 5, asecond catheter 50 b is advanced through sheath 46, such that secondcatheter 50 b is disposed alongside first guide member 56 a withinsheath 46. It is to be noted that, in both FIG. 1B and FIG. 5, twoanchors 48 are anchored at respective ventricular sites, and tworespective guide members 56, extend from the anchors, through atrium 6,and typically out of the body of the subject.

Reference is made to FIG. 6, which is a schematic illustration of asystem 180 for use with prosthetic valve support 42, in accordance withsome applications of the invention. For such applications of theinvention, prosthetic valve support 42 is slidable toward native valve10 over guide members 56, including while the prosthetic valve supportis compressed within delivery tube 80. Following coupling of anchors 48to the ventricular sites, guide members 56 extend from the anchors tooutside of the body of the subject, and have respective free proximalends 57. Before introduction of support 42 within tube 80 into the bodyof the subject (e.g., into sheath 46), guide members 56 are threadedthrough holes 82 in upstream support portion 43 of prosthetic valvesupport 42, and through delivery tube 80, e.g., by the operatingphysician.

FIGS. 3A-C and the descriptions thereof describe prosthetic valvesupport 42 being provided as a unit 140 comprising introducer tubes 144,which are removed subsequently to advancement of guide members 56through upstream support portion 43 and prior to introduction of theunit into the body of the subject. FIG. 6 shows system 180, in whichprosthetic valve support is provided within delivery tube 80, e.g., as aunit 182, coupled to a distal end of controller 142, describedhereinabove.

Unit 182 comprises (e.g., is provided having) one or more introducertubes 184, each introducer tube being shaped to define a lumentherethrough, and having an open distal end 183. Distal end 183 of eachtube is disposed outside a distal end of support 42 and/or tube 80, andeach introducer tube 184 extends out of a proximal end of the supportand/or tube 80. Similarly to unit 140 described with reference to FIGS.3A-C, each introducer tube 144 of system 180 passes from the distal endthereof, through a respective hole in upstream support portion 43 fromthe downstream surface of the support portion (which defines an outersurface of the support portion in the compressed state thereof) to anupstream surface of the support portion (which defines an inner surfaceof the support portion in the compressed state thereof). In contrast tounit 140, introducer tubes 184 extend from a proximal end of deliverytube 80 to a proximal end portion of the apparatus. In further contrastto unit 140, tubes 184 remain in place as unit 182 is advancedtransluminally over guide members 56. Tubes 184 are typically flexibleto facilitate transluminal advancement thereof.

A locking member 190 is disposed over each introducer tube 184, suchthat the introduction of guide member 56 through the introducer tubealso introduces the guide member through the locking member. Lockingmember 190 is slidable over guide member 56 (e.g., over tubular member100 thereof), and is configured to lock to longitudinal member 102.Typically, locking member 190 is identical to locking member 110,described hereinabove, except that locking member 190 is configured(e.g., dimensioned) to be slidable also over introducer tube 184. Eachlocking member 190 is disposed at the distal end of a respective tubularcontrol rod 192, which is typically identical to control rod 86,described hereinabove, except that control rod 192 is configured (e.g.,dimensioned) to be slidable also over introducer tube 184.

The use of system 180, including introducer tubes 184, advantageously(1) removes the requirement for two separate introductions of proximalend 57 of guide member 56 (i.e., through an introducer tube andsubsequently through a locking member and control rod); and (2)facilitates control rods 192 (and locking members 190) being present inthe atrium of the subject during expansion of prosthetic valve support42, thereby reducing an interval between the expansion of the prostheticvalve support and pressing of the prosthetic valve support against theannulus of the native valve.

Reference is made to FIGS. 7A-C, which are schematic illustrations of asystem 200 for facilitating transluminal delivery of a prosthetic valveassembly 202, in accordance with some applications of the invention.FIG. 7A shows prosthetic valve assembly 202 in an expanded statethereof. Prosthetic valve assembly comprises (1) a prosthetic valve body204, which comprises a first frame 206 (e.g., a wire frame), and isshaped to define a lumen 208 therethrough, (2) an annular upstreamsupport 210, which comprises a second frame 212 (e.g., a wire frame), isshaped to define an opening through the upstream support, and isconfigured to be placed against an upstream surface (e.g., an atrialsurface) of native valve 10 (e.g., of an annulus thereof), and (3) aflexible sheet 214 that couples the first frame to the second frame. Inthe expanded state of assembly 202 (and thereby of body 204), frame 206of body 204 is generally cylindrical, and has a diameter d1. In theexpanded state of assembly 202 (and thereby of upstream support 210),frame 212 of support 210 is typically generally annular, and has anouter perimeter 213 that has a diameter d2, which is greater thandiameter d1.

Sheet 214 may be a fabric, a film, and/or another sheet-like structure,and may comprise a natural material, a polymer, a biomaterial, and/orany other suitable material. Typically, sheet 214 comprises polyester,PTFE, and/or pericardial tissue.

For some applications, and as shown in FIG. 7A, in the expanded state ofassembly 202, and in the absence of external forces (e.g., if theassembly were resting on a table surface), sheet 214 is generallyannular and flat, and an upstream end 218 of frame 206 is disposedgenerally on a plane defined by support 210. For such applications, aninner perimeter 211 of frame 212 defines an opening that has a diameterd3 that is greater than diameter d1.

For some applications, in such an expanded and unconstrained state,sheet 214 is generally frustoconical or funnel-shaped, and upstream end218 of frame 206 is disposed below the plane defined by support 210.(For some such frustoconical or funnel-shaped arrangements, the sheetmay also be considered to be annular.)

For some applications, in such an expanded and unconstrained state,sheet 214 is generally tubular, upstream end 218 of frame 206 isdisposed below the plane defined by support 210. For such applications,diameter d3 is typically generally equal to diameter d1.

Typically, one or both of frames 206 and 212 is covered on at least oneside by a covering 220. For some applications, sheet 214 comprises aportion of covering 220, e.g., the sheet is defined by a portion of thecovering that is disposed between frames 206 and 212. For someapplications, and as shown in FIG. 7A, covering 220 is disposed (1) on atissue-facing side of frame 212 (e.g., defines a tissue-contactingsurface of support 210), and (2) on an inner surface of frame 206 (i.e.,lines the frame, and defines lumen 208).

A valve member 205 (e.g., comprising one or more prosthetic leaflets;shown in FIGS. 8D-G) is coupled to frame 206, is disposed within lumen208, and provides valve (e.g., one-way) functionality to assembly 202.Valve member 205 may alternatively or additionally comprise a differentvalve member, such as a mechanical valve member.

At least two eyelets 222 are disposed on an outer surface of body 204(i.e., protrude radially outward from body 204). Typically, eyelets 222are pivotably coupled to body 204, e.g., such that the eyelets can pivot(e.g., rotate) in both directions by at least 5 degrees (e.g., more than5 degrees and/or less than 90 degrees, such as between 5 and 90 degrees,e.g., between 5 and 60 degrees, such as between 5 and 45 degrees). Forsome applications, the eyelets can pivot in a plane parallel to a planedefined by a tangent of the valve body at the site to which the eyeletis coupled, as shown in the blowup box. Alternatively or additionally,the eyelets can pivot in a plane that is orthogonal to the plane definedby the tangent, e.g., such that the eyelets can point toward and/or awayfrom the valve body. For some applications, eyelets 222 are sutured tobody 204. Eyelets 222 are arranged in at least one pair; each eyelet ofthe pair being disposed on the opposite side of body 204 from the othereyelet of the pair.

FIG. 7B shows system 200 in a delivery configuration thereof. System 200comprises a delivery tool 230, which comprises a first housing 232(e.g., a proximal housing) and a second housing 234 (e.g., a distalhousing), which are articulatably coupled to each other via a flexiblecontrol rod assembly 240 disposed through the housings.

In the delivery configuration of system 200, assembly 202 is in acompressed state thereof, in which prosthetic valve body 204 (in acompressed state thereof) is generally cylindrical, and upstream support210 (in a compressed state thereof) is also generally cylindrical.Typically, in the delivery configuration of system 200, sheet 214 isalso generally cylindrical. Assembly 202, in the compressedconfiguration thereof, (1) has a central longitudinal axis, at one zone(e.g., at one end) of which body 204 is disposed, and at another zone(e.g., the other end) of which support 210 is disposed, and (2) definesan articulation zone 236 in which (a) at least part of sheet 214 isdisposed, and (b) neither frame 206 of body 204 nor frame 212 of support210 is disposed, and about which body 204 and support 210 arearticulatable with respect to each other.

In the delivery configuration of system 200, at least part of support210 is disposed within housing 232 (which maintains the at least part ofthe support in the compressed state thereof), and at least part of body204 is disposed within housing 234 (which maintains the at least part ofthe support in the compressed state thereof). Housing 232 defines anorifice 233 through which support 210 is introducible into the housing,and removable from the housing. Housing 234 defines an orifice 235 thatfaces orifice 233, and through which body 204 is introducible into thehousing, and removable from the housing. In the delivery configuration,eyelets 222 protrude radially outward beyond the surface of deliverytool 230 (e.g., beyond a lateral wall of housing 234). Typically,housing 234 (e.g., the lateral wall thereof) is shaped to define arespective slit 237 for each eyelet, through which the eyelet protrudesbeyond the surface of the housing. Each slit 237 is continuous with(i.e., is in communication with) orifice 235 such that, as describedhereinbelow, during deployment of valve body 204, eyelet 222 can slideout of the slit at the orifice.

In the delivery configuration of system 200, tool 230 is in a contractedstate, in which housing 232 is disposed at a distance d4 from housing234 (e.g., orifice 233 is disposed at distance d4 from orifice 235).Distance d4 is typically greater than 1.5 mm and/or less than 30 mm,such as between 1.5 mm and 30 mm (e.g., between 10 and 15 mm). In thisstate, at least part of sheet 214 is exposed between the housings. Theat least part of sheet 214 (and thereby of articulation zone 236) thatis exposed between housings 232 and 234 facilitates articulation ofhousing 234 containing body 204 with respect to housing 232 containingsupport 210, and thereby defines an articulation zone 238 of system 200in the delivery configuration thereof. Typically, at least part ofcontrol rod assembly 240 is flexible, so as to facilitate articulationat articulation zone 238. For example, although assembly 240 as a wholeis typically sufficiently flexible so as to facilitate its transluminaldelivery to the heart, control rods 244 and 246 may be more flexiblethan control rod 242 (e.g., more flexible than required for transluminaldelivery to the heart alone), so as to facilitate articulation atarticulation zone 238. For some such applications, respective portionsof control rods 244 and 246 that are disposed within articulation zone238 when tool 230 is in the contracted state (FIG. 7C) are more flexiblethan adjacent portions of the control rods (e.g., portions disposedwithin housings 232 and 234 when tool 230 is in the contracted state).For example, and as shown, a portion 245 of control rod 244 may benarrower than adjacent portions of the control rod.

Control rod assembly 240 comprises (1) a first housing-control rod 242,coupled to first housing 232, (2) a second housing-control rod 244,coupled to second housing 234, and (3) a prosthesis-control rod 246,coupled to a mount 248 that is reversibly couplable to valve assembly202, e.g., via a plurality of recesses 250 in the mount which receiverespective portions of assembly 202. Typically, assembly 202 iscouplable to mount 248 by valve body 204 being coupled to the mount, andfurther typically by a plurality of protrusions 252 of frame 206 beingdisposed within respective recesses 250. Housing 234 retains thiscoupling by inhibiting body 204 from expanding radially away from mount248.

Typically, at least part of second housing-control rod 244 is disposedwithin and slidable through prosthesis-control rod 246, and at leastpart of the prosthesis-control rod is disposed within and slidablethrough first housing-control rod 242 (e.g., coaxially).

System 200 (e.g., tool 230 thereof) further comprises at least twoflexible reference-force tubes 260, which extend, (a) from a proximalend of the system (e.g., from an extracorporeal portion of the system,such as from a handle of tool 230), (b) through a proximal end ofhousing 232, (c) through a lumen 254 defined by support 210 in thecompressed state thereof, (d) through sheet 214, (e) along the outsideof at least part of body 204, and typically (f) until a distal portionof body 204. A locking member 262 is disposed between each eyelet 222and a respective tube 260. Typically, locking members 262 are notdirectly coupled to body 204, but are instead each held in positionbetween eyelet 222 and tube 260 by a guide member 256 being disposedthrough the eyelet, the tube, and the locking member. For someapplications, locking member 262 is integral with eyelet 222 (e.g.,eyelet 222 is configured to and/or shaped to define locking member 262).

For some applications, guide members 256 are identical to guide members56, described hereinabove. Guide members 256 are described in moredetail hereinbelow.

Reference is now made to FIGS. 8A-H, which are schematic illustrationsof a technique for use with system 200, to transluminally implantprosthetic valve assembly 202, in accordance with some applications ofthe invention. Typically, sheath 46 is advanced transluminally (e.g.,transfemorally) to right atrium 12 of heart 4, through the fossa ovalis,and into left atrium 6 using standard transseptal techniques, asdescribed hereinabove with reference to FIGS. 1A-B. Subsequently, firsttissue anchor 48 a and second tissue anchor 48 b are anchored atrespective ventricular sites, e.g., as described with reference to FIGS.1A-B and/or 5, mutatis mutandis.

A guide member 256 is coupled to each tissue anchor (e.g., the tissueanchors are provided pre-coupled to the guide members), such that afteranchoring of the tissue anchors, each guide member extends from theanchor, out of the body of the subject, e.g., as described hereinabovewith respect to guide member 56, mutatis mutandis. A proximal end ofeach guide member 256 is introduced through a respective eyelet 222,locking member 262, and reference-force tube 260, such that system 200appears as shown in FIG. 7B. As described hereinabove, each guide member256 typically holds each locking member 262 in place between itsrespective eyelet 222 and reference-force tube 260.

System 200 (e.g., assembly 202 within delivery tool 230) is subsequentlyadvanced along guide members 256 and via sheath 46 to left atrium 6(FIG. 8A). Once exposed outside of the distal end of sheath 46, system200 is guided by guide members 256 generally toward the ventricularsites at which anchors 48 are anchored. Articulation of system 200(e.g., at articulation zone 238, and/or at another articulation zone 239proximal to housing 232) facilitates transluminal advancement of thesystem past curves in the vasculature. The articulation also facilitatesmovement of system 200 from the distal end of sheath 46 and betweenleaflets 14 of valve 10, e.g., by facilitating steering of the systemalong a path defined by guide members 256. This steering is typicallyfurther facilitated by (1) the position of eyelets 222 at a distalportion of system 200 (e.g., at a distal portion of housing 234), whichturns the housing in response to encountering a turn in members 256,and/or (2) the pivotable coupling of eyelets 222 to body 204, describedhereinabove; pivoting of eyelet 222 reduces a likelihood of the eyeletsnagging on guide member 256 when encountering a turn in the guidemember. For some applications, eyelets 222 are internally coated with amaterial having a low coefficient of friction, such aspolytetrafluoroethylene, to further facilitate sliding of the eyeletover guide member 256.

It is to be noted that, due to the described articulation, a distance d5between a proximal end of housing 232 and a distal end of housing 234may be greater than for a similar system that does not articulate. Forexample, distance d5 may be greater than a distance d6 along anatrioventricular axis between (a) a height on the atrioventricular axisof the upstream surface of native valve 10, and (b) a height on theatrioventricular axis of the transseptal entry point into left atrium 6(e.g., the fossa ovalis). For some applications, distance d5 may begreater than the overall height of left atrium 6. Distance d5 istypically greater than 25 mm and/or less than 100 mm, such as between 25mm and 100 mm (e.g., 35-60 mm, such as 40-50 mm).

Reference is made to FIG. 8B. System 200 is advanced such that distalhousing 234, containing valve body 204 in the compressed state thereof,passes between leaflets 14 of native valve 10. Valve body 204 iswithdrawn out of orifice 235 of housing 234 by moving control rod 244with respect to control rod 246. For example, and as shown in FIGS.8B-C, control rod 244 (and thereby housing 234) may be moved distallyinto ventricle 8, while control rod 246 (and thereby mount 248 and valvebody 204) remains stationary, thereby increasing the distance betweenhousing 232 and housing 234.

When protrusions 252 of frame 206 become withdrawn from housing 234, theportion of valve body 204 coupled to the mount expands (e.g.,automatically), thereby disengaging the protrusions from recesses 250 ofmount 248, and decoupling the valve body from the mount (FIG. 8C). Forclarity, FIGS. 8C-D show the distal portion of valve body 204 expandingbefore the proximal portion of the valve body. It is to be noted,however, that portions of the valve body typically expand as they becomeexposed from housing 234, and therefore the proximal portion of thevalve body typically expands while the distal portion of the valve bodyis still disposed within housing 234.

FIG. 8D shows valve body 204 having been completely removed from housing234, and support 210 having been removed from proximal housing 232 bycontrol rod 242 (and thereby housing 232) being withdrawn proximally,thereby further increasing the distance between housing 232 and housing234. Typically, an opposing reference force is provided byreference-force tubes 260, so as to hold assembly 202 in place at thenative valve while housing 232 is withdrawn.

During the withdrawal of valve body 204 from housing 234, eyelets 222typically slide through slits 237, and out of the slits at orifice 235.

For some applications, support 210 is deployed from housing 232 beforevalve body 204 is deployed from housing 234.

Subsequently, tension is applied to guide members 256 while an opposingreference force is provided to assembly 202 by tubes 260, therebyreducing a length of each guide member 256 that is disposed betweeneyelet 222 and its respective tissue anchor 48 (FIG. 8E). That is, eachguide member 256 is slid proximally with respect to its respectivereference-force tube 260. Typically, the reference-force is provided toassembly 202 by a distal end of each reference-force tube 260 abutting arespective locking member; the reference force being transferred via thelocking member (and typically further via eyelet 222 to valve body 204).

For some applications this tensioning moves valve body 204 at leastslightly distally into ventricle 8, such that sheet 214 becomes at leastslightly frustoconical (e.g., as shown in FIG. 8E). For someapplications this tensioning deforms support 210 and/or deflects thesupport with respect to body 204, e.g., such that the support becomesless flat (e.g., less planar). For example, before tensioning, support210 may be flat annular (as shown in FIG. 8D), and after tensioning thesupport may be frustoconical (as shown in FIG. 8E). Alternatively, andas described in more detail with reference to FIGS. 14A-B, mutatismutandis, the prosthetic valve assembly may be configured such that theupstream support is frustoconical before tensioning, and the tensioningchanges a slant of the frustoconical shape. For example, beforetensioning, the upstream support may be frustoconical with the largerbase of the frustum closer to a ventricular end of an atrioventricularaxis than is the smaller base of the frustum, and after tensioning thesupport may become flatter, or may even invert, such that it becomesfrustoconical with the smaller base closer to the ventricular end of theatrioventricular axis (e.g., the conformation shown in FIG. 8E, mutatismutandis).

For some applications, tensioning is performed before deployment ofsupport 210 from housing 232.

Each guide member 256 typically comprises a tether 282 (e.g., alongitudinal member), a pull-wire 284, and a tubular member 280 in whichthe pull-wire and the tether are disposed. A distal portion of pull-wire284 is reversibly coupled to a proximal portion of tether 282, andtubular member 280 fits snugly over at least the distal portion of thepull-wire and the proximal portion of the tether so as to inhibit thepull-wire from becoming decoupled from the tether (e.g., to maintain astate of coupling therebetween). For some applications, and as shown,the reversible coupling is provided by pull-wire 284 and tether 282defining respective mating surfaces. For some applications, thereversible coupling is provided as described hereinabove for guidemember 56.

When each guide member 256 (e.g., the tether 282 thereof) is tensioned,the guide member is withdrawn proximally until at least part of tether282 (within tubular member 280) is disposed within locking member 262(e.g., at least until the proximal portion of the tether has passedthrough the locking member; FIG. 8E state B).

Reference is now made to FIG. 8F. Once a desired tension is obtained,the tension is fixed. Tubular member 280 is withdrawn proximally withrespect to tether 282, pull-wire 284 and locking member 262 (FIG. 8F).State A of FIG. 8F shows tubular member 280 having been withdrawn untileyelet 222. State B of FIG. 8F shows tubular member 280 having beenwithdrawn until a distal end of the tubular member is disposed proximalto locking member 262, thereby exposing tether 282 to the lockingmember.

Typically, locking member 262 is biased (e.g., shape-set) to assume alocked state, and while tubular member 280 is disposed within thelocking member, the tubular member inhibits locking of the lockingmember to tether 282 (or to pull-wire 284), and the removal of thetubular member from within the locking member facilitates automaticlocking of the locking member to the tether (i.e., transitioning of thelocking member into a locked state). Tubular member 280 is slidablethrough locking member 262 despite such biasing of the locking member,e.g., due to (a) the tubular member having a smooth surface, and/or (b)the tubular member retaining locking elements 263 of the locking memberat an angle alpha_1 with respect to the tubular member, which isshallower than an angle alpha_2 with respect to tether 282 that thelocking elements assume when the tubular element is withdrawn (compareFIG. 8F state A to state B).

Typically, tether 282 defines a plurality of nodules 286, whichfacilitate locking of locking member 262 to the tether. For someapplications, locking elements 263 and nodules 286 function as aratchet. For some such applications, subsequently to transitioning oflocking member 262 into the locked state thereof, one-way movement oftether 282 through the locking member is possible, thereby facilitatingfurther increase, but not reduction, of tension.

Reference is now made to FIG. 8G. Tubular member 280 and pull-wire 284are decoupled from tether 282 and prosthetic valve assembly 202, anddelivery tool 230 is withdrawn proximally (e.g., into sheath 46, and outof the body of the subject). Typically, housing 234 and mount 248 arewithdrawn via the lumen of valve body 204 (e.g., between the prostheticleaflets disposed therein). For some applications, housing 234, rods 244and 246, and mount 248 are withdrawn prior to the tensioning step (e.g.,prior to withdrawal of reference-force tubes 260, such as between thestep shown in FIG. 8D and the step shown in FIG. 8E, mutatis mutandis).

Typically, tubular member 280 and pull-wire 284 are decoupled fromtether 282 by withdrawing the tubular member further proximally, suchthat the distal portion of pull-wire 284 and the proximal portion oftether 282 are exposed from the tubular member (state A of FIG. 8G).Reference force for this withdrawal is provided by the anchored tether282, and optionally also by reference-force tubes 260. Tubular member280, pull-wire 284, and reference-force tube 260 are then withdrawn(state B of FIG. 8H).

FIG. 8H is a schematic illustration of prosthetic valve assembly 202following implantation at native valve 10 of heart 4. Assembly 202provides replacement one-way valve functionality in which blood flowsfrom atrium 6, through the opening defined by upstream support 210, pastsheet 214, through lumen 208 of valve body 204, and into ventricle 8.Sheet 214 thereby defines and/or serves as a conduit that provides fluidcommunication between the opening defined by upstream support 210 (e.g.,by frame 212 thereof) and lumen 208 of valve body 204. Furthertypically, this conduit is uninterrupted except for holes (not shown)that may remain where reference-force tubes 260 originally extendedthrough the sheet.

Regurgitation through these holes is typically minimal or absent due totheir small size. The holes may be slit-like (rather than punchedholes), such that in the absence of reference-force tubes 260 the holesbecome generally closed. Additionally, coaptation of leaflets 14 andtissue growth over the holes may further facilitate sealing.Alternatively or additionally, the holes may be defined by tubularprotrusions 215 that extend from sheet 214 (shown in the “optional” box,FIG. 7B). Tubular protrusions 215 may comprise the same material assheet 214, or may comprise a different material. Tubular protrusions 215may be flexible or rigid. The tubular protrusions are configured toprovide a channel through which tubes 260 may pass, but which, in theabsence of tubes 260, inhibit movement of fluid therethrough. Forexample, tubular protrusions 215 may inhibit fluid flow due to the ratiobetween their length and lumen diameter, and/or may act as duckbillvalves. Therefore, sheet 214 typically provides a generally sealedconduit between upstream support 210 and valve body 204.

The positioning of prosthetic valve assembly 202 at the native valvetypically results in leaflets 14 of the native valve coapting aroundvalve body 204, thereby providing sealing that inhibits (e.g., prevents)perivalvular leakage.

The positioning of prosthetic valve assembly typically also places sheet214 in contact with the annulus and/or leaflets of the native valve. Ingeneral, a prosthetic valve implanted at a native valve encountersforces due to beating of the heart and/or the resulting flow of blood.Small movements (e.g., oscillations) resulting from these forces mayinhibit tissue growth (e.g., fibrosis) that would otherwise facilitatesealing between the prosthetic valve and the native valve. For someapplications, such movements are reduced (e.g., dampened) at sites atwhich the contact between assembly 202 and the surrounding tissue isprovided by sheet 214, e.g., due to flexibility of the sheet. Therebysheet 214 typically provides stabilized (e.g., more constant) contactwith tissue than would a less flexible structure in the same position;this is hypothesized to improve tissue growth and thereby sealing.Furthermore, sheet 214 itself may be configured to promote tissue growththereon, e.g., due to surface treatments and/or impregnation, and/orstructure, such as weave and/or porosity, thereby further facilitatingsealing.

Reference is made to FIGS. 9A-14B, which are schematic illustrations ofprosthetic valve assemblies, in accordance with some applications of theinvention. Each prosthetic valve assembly shown in FIGS. 9A-14Bcomprises a valve body, an upstream support, and a sheet, which aretypically identical, mutatis mutandis, to valve body 204, upstreamsupport 210 and sheet 214 described hereinabove, except for where noted.

FIGS. 9A-B show, prosthetic valve assembly 202 described hereinabove, ina simplified (e.g., two-dimensional) schematic manner that illustratesthe arrangement of valve body 204, upstream support 210 and sheet 214,in the compressed state (FIG. 9A) and the expanded (e.g., implanted)state (FIG. 9B). FIGS. 9A-B are included at least in part in order tofacilitate interpretation of the simplified schematic illustrations ofthe prosthetic valve assemblies of FIGS. 10A-14B. FIG. 9A, like FIGS.10A, 11A, 12A and 13A, shows the prosthetic valve assembly in thecompressed state as if it were contained in the delivery tool thereof(e.g., tool 230), but for clarity does not show the delivery tool.Typically, sheet 214 is attached at least to inner perimeter 211 ofupstream support 210, and to an upstream end 207 of frame 206 of valvebody 204.

FIGS. 10A-B show a prosthetic valve assembly 302, which comprises avalve body 304 comprising a first frame 306, an upstream support 310comprising a second frame 312, and a flexible sheet 314. In the expandedstate of support 310 (FIG. 10B), frame 312 defines an outer perimeter313 and an inner perimeter 311 that defines an opening through thesupport. During implantation, support 310 is placed against the upstreamsurface of the native valve, and valve body 304 is subsequentlyintracorporeally coupled (e.g., directly coupled) to the support bybeing expanded within the opening of the support, e.g., as describedhereinabove with reference to FIG. 1F, mutatis mutandis.

Sheet 314 is not attached to inner perimeter 311 of frame 312, butrather is circumferentially attached to frame 312 at a radius that isgreater than that of the inner perimeter. For example, sheet 314 may beattached to frame 312 at outer perimeter 313. Sheet 314 is also notattached to an upstream end 307 of valve body 304. Thereby a pocketregion 316 is defined between sheet 314 and at least inner perimeter311, in which sheet 314 is not attached to frame 312 or frame 306.

In the compressed state (FIG. 10A), sheet 314 is disposed alongside andoutside at least part of frame 312 and at least part of frame 306. Frame312 is configured such that when the frame is in the compressed state,inner perimeter 311 defines a downstream end of the frame (e.g., of thecylindrical shape of the frame), and outer perimeter 313 defines anupstream end. Therefore, when frame 312 expands, the upstream end of theframe expands radially outward more than does the downstream end of theframe.

FIGS. 11A-B show a prosthetic valve assembly 342, which comprises avalve body 344 comprising a first frame 346, an upstream support 350comprising a second frame 352, and a flexible sheet 354. In the expandedstate of support 350 (FIG. 11B), frame 352 defines an outer perimeter353 and an inner perimeter 351 that defines an opening through thesupport. During implantation, support 350 is placed against the upstreamsurface of the native valve, and valve body 344 is subsequentlyintracorporeally coupled (e.g., directly coupled) to the support bybeing expanded within the opening of the support, e.g., as describedhereinabove with reference to FIG. 1F, mutatis mutandis.

Sheet 354 is not attached to inner perimeter 351 of frame 352, butrather is circumferentially attached to frame 352 at a radius that isgreater than that of the inner perimeter. For example, sheet 354 may beattached to frame 352 at outer perimeter 353. Sheet 354 is also notattached to an upstream end 347 of valve body 344. Thereby a pocketregion 356 is defined between sheet 354 and at least inner perimeter351, in which sheet 354 is not attached to frame 352 or frame 346.

Frame 352 is configured such that when the frame is in the compressedstate, the frame has a generally cylindrical shape that defines a lumentherethrough, inner perimeter 351 defines an upstream end of the frame(e.g., of the cylindrical shape of the frame), and outer perimeter 353defines a downstream end. Therefore, when frame 352 expands, thedownstream end of the frame expands radially outward more than does theupstream end of the frame. In the compressed state (FIG. 11A), sheet 354is disposed alongside and outside of at least part of frame 346, andthrough at least part of the lumen defined by frame 352.

FIGS. 12A-B show a prosthetic valve assembly 382, which comprises avalve body 384 comprising a first frame 386, an upstream support 390comprising a second frame 392, and a flexible sheet 394. In the expandedstate of support 390 (FIG. 12B), frame 392 defines an outer perimeter393 and an inner perimeter 391 that defines an opening through thesupport. Frame 392 is coupled to frame 386 prior to implantation (e.g.,assembly 382 is provided with frame 392 coupled to frame 386). For someapplications, frames 392 and 386 are integral, e.g., are defined byrespective regions of a single frame. During implantation, valve body384 is advanced between leaflets of the native valve, and support 390 isplaced against the upstream surface of the native valve (e.g., asdescribed with reference to FIGS. 8B-D, mutatis mutandis.

Sheet 394 is not attached to inner perimeter 391 of frame 392, butrather is circumferentially attached to frame 392 at a radius that isgreater than that of the inner perimeter. For example, sheet 394 may beattached to frame 392 at outer perimeter 393. Sheet 394 is also notattached to an upstream end 387 of valve body 384. Thereby a pocketregion 396 is defined between sheet 394 and at least inner perimeter391, in which sheet 394 is not attached to frame 392 or frame 386.

Assembly 382 is configured such that, in the compressed state thereof(FIG. 12A), frames 386 and 392 are generally collinear, and form agenerally continuous cylinder. Frame 392 is configured such that in thecompressed state, outer perimeter 393 defines an upstream end of theframe (and thereby of assembly 382). Therefore, when frame 392 expands,the upstream end of the frame expands radially outward more than doesthe downstream end of the frame. In the compressed state, sheet 394 isdisposed alongside and outside of at least part of frame 386, and atleast part of frame 392.

FIGS. 13A-B show a prosthetic valve assembly 402, which comprises avalve body 404 comprising a first frame 406, an upstream support 410comprising a second frame 412, and a flexible sheet 414. In the expandedstate of support 410 (FIG. 13B), frame 412 defines an outer perimeter413 and an inner perimeter 411 that defines an opening through thesupport. Frame 412 is coupled to frame 406 prior to implantation (e.g.,assembly 402 is provided with frame 412 coupled to frame 406). For someapplications, frames 412 and 406 are integral, e.g., are defined byrespective regions of a single frame. During implantation, valve body404 is advanced between leaflets of the native valve, and support 410 isplaced against the upstream surface of the native valve (e.g., asdescribed with reference to FIGS. 8B-D, mutatis mutandis.

Sheet 414 is not attached to inner perimeter 411 of frame 412, butrather is circumferentially attached to frame 412 at a radius that isgreater than that of the inner perimeter. For example, sheet 414 may beattached to frame 412 at outer perimeter 413. Sheet 414 is also notattached to an upstream end 407 of valve body 404. Thereby a pocketregion 416 is defined between sheet 414 and at least inner perimeter411, in which sheet 414 is not attached to frame 412 or frame 406.

Assembly 402 is configured such that, in the compressed state thereof(FIG. 13A), frame 412 is disposed generally alongside at least a portionof frame 406. Frame 412 is configured such that in the compressed state,outer perimeter 413 defines a downstream end of the frame. Therefore,when frame 412 expands, the downstream end of the frame expands radiallyoutward more than does the upstream end of the frame. In the compressedstate, sheet 414 is disposed alongside and outside of at least part offrame 406.

FIGS. 14A-B show a prosthetic valve assembly 422 an expanded statethereof, implanted at native valve 10, in accordance with someapplications of the invention. Assembly 422 comprises a valve body 424comprising a first frame 426, an upstream support 430 comprising asecond frame 432, and a sheet 434.

Frame 426 of valve body 424 has an upstream end 427 and a downstream end429. In the expanded state, in the absence of external forces, an outerperimeter 433 of second frame 432 of upstream support 430 is disposedcloser to downstream end 429 than is an inner perimeter 431 of thesecond frame. For example, upstream support 430 may define a frustum,the larger base of which is disposed closer to downstream end 429 (andcloser to a ventricular end of an atrioventricular axis) than is thesmaller base of the frustum. For some applications, the assembly is thusconfigured such that, when placed at the native valve, outer perimeter433 of the upstream support contacts the upstream surface of the nativevalve (e.g., the valve annulus), and the inner perimeter of the upstreamsupport does not (FIG. 14A). For some such applications, frame 432 maybe flat annular in the absence of external forces, and in the expandedstate, sheet 434 retains the second frame in the frustoconical shape byinhibiting expansion of the second frame (e.g., expansion of at leastouter perimeter 433 thereof). For some applications, frame 432 curvesdownward toward the tissue that outer perimeter 433 contacts(configuration not shown).

Sheet 434 is not attached to inner perimeter 431 of frame 432, butrather is circumferentially attached to frame 432 at a radius that isgreater than that of the inner perimeter. For example, sheet 434 may beattached to frame 432 at outer perimeter 433. Sheet 434 is also notattached to upstream end 427 of valve body 424. Thereby a pocket region436 is defined between sheet 434 and at least inner perimeter 431, inwhich sheet 434 is not attached to frame 432 or frame 426.

For some such applications, such a configuration provides a springfunctionality that allows valve body 424 to move along anatrioventricular axis while outer perimeter 433 and/or portions of sheet434 remain in contact with tissue (FIG. 14B). For example, assembly 422may be implanted using techniques described with reference to FIGS.8A-H, mutatis mutandis, and the spring functionality may allow movementof valve body 424 ventricularly during tensioning of tethers 282 whilemaintaining contact between outer perimeter 433 and the atrial surface.Similarly, such a configuration may allow oscillation of valve body 424along the atrioventricular axis (e.g., caused by beating of the heartand the resulting blood flow), while maintaining constant contactbetween outer perimeter 433 and the tissue.

For some applications, a compressed state of assembly 422 is asdescribed for one or more of the prosthetic valve assemblies describedwith reference to FIGS. 10A-13B, mutatis mutandis. For example, for someapplications frame 426 of body 424 is coupled to frame 432 of support430 prior to implantation (e.g., assembly 422 is provided with frame 426coupled to frame 432), such as described for assembly 382 and/orassembly 402, mutatis mutandis. Alternatively, frame 426 isintracorporeally coupled to frame 432, e.g., as described for assembly302 and/or assembly 342, and/or with reference to FIG. 1F, mutatismutandis.

For some applications, assembly 422 is implanted as described for one ormore of the prosthetic valve assemblies described with respect to FIGS.10A-13B, mutatis mutandis.

Reference is again made to FIGS. 9A-B, 10A-B, and 11A-B. As describedhereinabove, in its compressed state, assembly 202 defines anarticulation zone in which (a) at least part of sheet 214 is disposed,and (b) neither frame 206 of body 204 nor frame 212 of support 210 isdisposed, and about which body 204 and support 210 are articulatablewith respect to each other. It is to be noted that in their compressedstates, assemblies 302 and 342 also define respective articulation zones336, 376. For each assembly, at least part of the respective sheet isdisposed in the articulation zone, neither the respective frame of thevalve body nor the respective frame of the support is disposed in thearticulation zone, and the respective valve body and support arearticulatable with respect to each other, about the articulation zone.

Reference is again made to FIGS. 10A-B, 11A-B, 12A-B, 13A-B, and 14A-B.As described hereinabove, assemblies 302, 342, 382, 402 and 422 eachdefine a respective pocket region between the respective sheet and atleast the inner perimeter of the frame of the upstream support. As alsodescribed hereinabove, (e.g., with reference to assembly 202), placementof the flexible sheet of the prosthetic valve assembly in contact withtissue provides stabilized contact with the tissue, and thereby improvestissue growth and sealing. Provision of a pocket region such as thosedescribed hereinabove is hypothesized to further improve sealing (e.g.,by further facilitating tissue growth). For example, such configurations(1) may provide a greater surface area of the flexible sheet and/or agreater tissue-contact area of the sheet (e.g., due to an angle of thesheet), and/or (2) may hold the flexible sheet under less tension (e.g.,compared to assembly 202), such that the sheet is freer to move withmovement of the valve assembly and/or tissue, thereby dampeningmovements that may otherwise inhibit tissue growth and/or sealing. Thisis illustrated in FIGS. 14A-B, which show an example of the contactbetween flexible sheet 434 and tissue (e.g., leaflets 14). For someapplications, the sheet is elastic, so as to further facilitatemaintenance of contact despite movement of the frames of the prostheticvalve assembly with respect to the native valve.

As described hereinabove, the respective pocket region of each assembly302, 342, 382, 402 and 422 is defined by the manner in which the sheetof the assembly is coupled to the frames of the assembly. When theassembly is in the expanded state thereof, the sheet is typicallyfrustoconical and/or funnel-shaped. This shape is defined by a lateralwall (i.e., the sheet itself), and first and second apertures (at eitherend of the shape), the first aperture being larger than the secondaperture. A portion of the sheet that defines the first aperture iscircumferentially attached to the frame of the upstream support at aradius that is greater than a radius of the inner perimeter of thesupport. A portion of the sheet that defines the second aperture iscircumferentially attached to the frame of the valve body at alongitudinal site that is closer to a downstream end of the valve bodythan is the longitudinal site at which the upstream support is coupledto the valve body.

For some applications, the sheet extends radially past the radius atwhich it is coupled to the upstream support. As described hereinabove,for some applications the sheet is coupled to the upstream support at anouter perimeter of the upstream support. For some applications, thesheet extends radially past the outer perimeter of the upstream support.

Reference is made to FIGS. 15A-C, which are schematic illustrations of atool 460 for facilitating application of force between prosthetic valveassembly 202 and guide members 256 (e.g., tethers 282 thereof), inaccordance with some applications of the invention. For someapplications, tool 460 serves as a tension-detector tool. For someapplications, tool 460 alternatively or additionally serves as atension-applicator tool.

The boxes on the right-hand side of FIGS. 15A-C shows assembly 202 beingimplanted at native valve 10, as described hereinabove. The box of FIG.15A shows assembly 202 having been deployed (e.g., delivered andexpanded) at the native valve, e.g., as described with reference to FIG.8D. The box of FIG. 15B shows tethers 282 of guide members 256 havingbeen tensioned with respect to assembly 202, e.g., as described withreference to FIG. 8E. The box of FIG. 15C shows tubular member 280 ofeach guide member 256 having been withdrawn proximally so as to (1)facilitate locking of the respective locking member 262 to itsrespective tether 282, e.g., as described with reference to FIG. 8F, and(2) decouple pull-wire 284 from tether 282, e.g., as described withreference to FIG. 8G.

The left-hand side of FIGS. 15A-C shows (1) a proximal end of system 200(e.g., a proximal end of delivery tool 230 thereof, e.g., including ahandle 231 thereof), including a proximal portion of pull-wire 284, aproximal portion of tubular member 280, and a proximal portion ofreference-force tube 260, and (2) tool 460 coupled to the proximalportion of pull-wire 284 and the proximal portion of reference-forcetube 260. The left-hand side of FIGS. 15A-C shows one tool 460 beingused with one pull-wire 284, tubular member 280, tube 260 and tool 460(and one handle 231). However, it is to be noted that tool 460 istypically used with each guide member (e.g., each tether 282), eithersequentially, or by providing more than one tool 460 for use atgenerally the same time.

Tool 460 comprises a pull-wire-coupling element 462, configured to becoupled to the proximal portion of pull-wire 284 (e.g., to a grip 464 ofthe pull-wire), and a reference-force-tube-coupling element 466,configured to be coupled to the proximal portion of reference-force tube260 (e.g., to a grip 468 of the tubular member). Coupling elements 462and 466 are coupled to each other via an adjustment member 470 thatfacilitates adjustment of a distance between the coupling elements.Adjustment member 470 may comprise screw threads, a ratchet mechanism,or any other suitable adjustment mechanism.

Pull-wire-coupling element 462 is coupled to the proximal portion ofpull-wire 284 (e.g., to a grip 464 of the pull-wire), andreference-force-tube-coupling element 466 is coupled to the proximalportion of reference-force tube 260 (e.g., to a grip 468 of the tubularmember), typically subsequently to delivery of prosthetic valve assembly202 to the native valve (FIG. 15A). A distance d7 exists betweencoupling elements 462 and 466.

Subsequently, adjustment member 470 is used (e.g., actuated) so as tochange (e.g., increase) the distance between coupling elements 462 and466 (FIG. 15B; distance d8). This reduces the length of tether 282 thatis disposed distal to the distal end of reference-force tube 260, (andthereby the length of the tether that is disposed between eyelet 222 andanchor 48), thereby applying tension to the tether). Typically, a lengthindicator 471 (e.g., a rule) is provided on tool 460 that indicates thechange in length that has been made. Further typically, tool 460comprises a force detector 472 that detects and displays a forcedifferential (e.g., a linear force differential) between couplingelements 462 and 466, and thereby provides an indication of the tensilestate of tether 282.

When a desired tensile state of tether 282 has been achieved (e.g., anabsolute value and/or a value relative to other detected forces, such asthe tensile state of the other tether 282), the tension is fixed, andpull-wire 284 is decoupled from tether 282 (FIG. 15C). As described withreference to FIG. 8F, this is achieved by withdrawing tubular member 280proximally with respect to tether 282, pull-wire 284 and locking member262. FIG. 15C shows a proximal portion of tubular member 280 (e.g., agrip 474 thereof) being withdrawn proximally with respect to (1)pull-wire 284 (and therefore with respect to tether 282 to which thepull-wire is coupled), and (2) reference-force tube 260 (and thereforewith respect to locking member 262 which the distal end of thereference-force tube abuts). This is illustrated by a distance d10between grips 468 and 474 in FIG. 15C, which is greater than a distanced9 between grips 468 and 474 in FIG. 15B. This thereby facilitates (1)locking of locking member 262 to tether 282, and (2) subsequently (i.e.,after further proximal withdrawal of the tubular member), decoupling ofpull-wire 284 from the tether.

For some applications, this is performed by one continuous movement oftubular member 280. For some applications, visual and/or tactileindicators allow the operating physician to lock locking member 262 totether 282 without decoupling pull-wire 284 from the tether. This mayadvantageously allow the physician to further increase the tension onthe tether (e.g., by using the ratchet functionality described withreference to FIG. 8F) before decoupling the pull-wire from the tether.

Although tool 460 is described hereinabove for facilitating implantationof assembly 202, the tool may also be used, mutatis mutandis, incombination with other systems described herein, such as system 40described hereinabove and/or assembly 552 described hereinbelow (e.g.,for tensioning tethers 582 thereof).

Reference is now made to FIG. 16, which is a schematic illustration of asystem 480 comprising a prosthetic valve assembly 482 and one or moresprings 484 via which the prosthetic valve assembly is elasticallycoupled to one or more tissue anchors 48, in accordance with someapplications of the invention. For illustrative purposes, system 480 isshown as comprising system 200 (e.g., comprising prosthetic valveassembly 202), described hereinabove, with the addition of springs 484.However, it is to be noted that the techniques described with referenceto FIG. 16 may alternatively or additionally be used to facilitateimplantation of other prosthetic valves and/or prosthetic valveassemblies described herein, mutatis mutandis (e.g., springs 484 may beadded to other prosthetic valves and/or prosthetic valve assembliesdescribed herein).

Each spring 484 is disposed outside of valve body 204, typicallylaterally outside the valve body, and further typically between eyelet222 and locking member 262 (e.g., coupling the eyelet to the lockingmember). For example, and as shown, spring 484 may have a longitudinalaxis that is generally parallel with lumen 208 of the valve body. Whenreference-force tube 260 provides the reference force to locking member262 during tensioning of guide member 256 (e.g., tether 282 thereof),the reference force is transferred via spring 484. Typically spring 484serves as a compression spring, such that increasing tension on guidemember 256 (e.g., the tether 282 thereof) compresses the spring.

For some applications, spring 484 provides an indication of a state ofthe spring that is observable and recognizable using imaging techniques(e.g., fluoroscopy). That is, spring 484 is configured to change shapein response to a force applied to it, in a manner that is observable andrecognizable using fluoroscopy. This functionality therefore providesintracorporeal measurement of tension on tether 282 (in a manner that isitself observable extracorporeally). It is hypothesized that for someapplications, this intracorporeal measurement advantageously detects thetension with reduced interference (e.g., noise) that may be present inextracorporeal measurement techniques. For example, for someapplications, extracorporeal measurement of the tension byextracorporeally measuring tension on pull-wire 284 (e.g., tension withrespect to reference-force tube 260) may be inhibited by interference byinherent elasticity of the pull-wire and other elements of the system,and by friction between elements of the system.

For some applications, the shape of spring 484 alone provides thetension indication. For such applications, spring 484 may be coated witha radiopaque material such as tantalum. For some applications, spring484 has (e.g., comprises and/or is coupled to) one or more radiopaquemarkers 486, and the juxtaposition of the markers facilitatesextracorporeal detection of the shape of the spring. For example, whenspring 484 serves as a compression spring, a reduction of a distance d11(compare d11 to d11′) between adjacent markers 486 indicates an increasein tension on tether 282.

For some applications, an intracorporeal reference (e.g., a scale) 488is provided, to facilitate identification of shape change of spring 484(e.g., to facilitate quantification of the shape change by (1) comparingthe position of markers 486 to reference 488, and/or (2) comparing thejuxtaposition of markers 486 to the juxtaposition of elements of thescale. For example, and as shown in FIG. 16, scale 488 may itself alsocomprise a plurality of radiopaque markers 490 disposed on valve body204 (e.g., coupled to frame 206) at known (e.g., regular) intervals, anddistance d11 (observed using fluoroscopy) is compared to a distance d12between adjacent markers 490 (observed using fluoroscopy) in order todetermine the actual change in distance d11. That is, an observedrelative change between d11 and d12 is used to determine an actualabsolute change in d11.

For some applications, spring 484 also alters the relationship between(a) changes in the length of tether 282 disposed between eyelet 222 andanchor 48 and (b) tension on the tether. For example, for system 200described hereinabove (i.e., in the absence of spring 484), startingwith slack on tether 282 between the eyelet and the anchor, as thelength of the tether between the eyelet and the anchor is reduced,tension on tether 282 may remain constant and low despite the reductionin the length of the tether, until the tether encounters resistanceprovided by tissue anchor 48, at which point tension increasesrelatively quickly for every unit reduction in length. For system 480(i.e., using spring 484), the relationship between (a) the length oftether 282 disposed between the eyelet and the anchor, and (b) thetension on the tether, is smoother (e.g., the transition between beforeand after resistance from the anchor is encountered is smoother). Thatis, spring 484 absorbs some of the applied tensile force and in exchangeprovides additional length to the tether. This is hypothesized toadvantageously provide more flexibility to the operating physician toadjust the length of tether 282 disposed between the eyelet and theanchor, with reduced changes to tension on the tether.

For some applications, spring 484 is configured so as to provide adesired tension (e.g., a desired resistance) over a range of lengths oftether 282 (e.g., over a range of compression states of the spring).That is, the spring constant of the spring is sufficiently low that achange in resistance is minimized per unit length change. For example,the spring constant may be less than 50 g/mm

For some applications, the desired tension is above 300 g force and/orbelow 700 g force, e.g., above 400 g force, and/or below 600 g force,such as between 400 g force and 600 g force, e.g., about 500 g force.For example, a desired target tether tension may be 500 g force, andspring 484 may be configured to provide, over a range of compressionstates of the spring, resistance that results in a tether tension thatis within a margin tension (e.g., within 200 g force, such as within 100g force) of the target force.

For some applications, spring 484 is configured to provide a distinctindication, observable using fluoroscopy, when the spring experiences aforce that is within a margin force (i.e., a force that corresponds tobeing within the margin tension). For example, spring 484 may undergo(e.g., suddenly undergo) a more obvious shape change when such a forceis experienced.

For some applications, spring 484 is configured to act as aconstant-force spring or similar, so as to facilitate the behaviordescribed above. For some applications, spring 484 is pre-loaded (e.g.,pre-tensioned or pre-compressed).

Reference is made to FIG. 17, which is a schematic illustration of asystem 500 comprising a prosthetic valve assembly 502 and one or moresprings 504 via which the prosthetic valve assembly is elasticallycoupled to one or more tissue anchors 48, in accordance with someapplications of the invention. For illustrative purposes, system 500 isshown as comprising system 200 (e.g., comprising prosthetic valveassembly 202), described hereinabove, with the addition of springs 504.However, it is to be noted that the techniques described with referenceto FIG. 17 may alternatively or additionally be used to facilitateimplantation of other prosthetic valves and/or prosthetic valveassemblies described herein, mutatis mutandis (e.g., springs 504 may beadded to other prosthetic valves and/or prosthetic valve assembliesdescribed herein).

Each spring 504 is disposed outside of valve body 204, typicallylaterally outside the valve body, and further typically is disposedfunctionally between locking member 262 and anchor 48 (e.g., betweenlocking member 262 and eyelet 222, or between eyelet 222 and anchor 48.For some applications, and as shown, spring 504 is a cantilever spring,and may be defined by a protrusion of frame 206 that extends away (e.g.,laterally away) from valve body 204. That is, spring 504 may comprise anelastically-deformable appendage. For some applications, the protrusionis shaped to define a loop 506 that provides spring 504 withconstant-force-spring functionality.

Typically, spring 504 provides similar functionality to spring 484,described hereinabove, mutatis mutandis. For example, for someapplications, spring 504 provides an indication of a state of the springthat is observable and recognizable using fluoroscopy. That is, spring504 is configured to change shape in response to a force applied to it,in a manner that is detectable and recognizable using fluoroscopy. Forsome applications, spring 504 also alters the relationship between (a)the length of tether 282 disposed between eyelet 222 and anchor 48 and(b) tension on the tether, e.g., as described hereinabove with referenceto spring 484, mutatis mutandis.

Reference is made to FIGS. 18A-B, which are schematic illustrations ofsprings coupled to tether 282 so as to elastically couple tissue anchor48 (e.g., a tissue-engaging element 49 thereof) to prosthetic valveassembly 202 (e.g., to valve body 204 thereof), in accordance with someapplications of the invention. FIG. 18A shows a spring 520 disposedpartway along tether 282. FIG. 18B shows a spring 530, one end of whichis coupled to anchor 48 (e.g., to an anchor head 47 thereof) and theother end of which is coupled to tether 282. Springs 520 and 530 aretypically tension springs. For some applications, spring 530 is rigidlycoupled to anchor head 47.

For illustrative purposes, springs 520 and 530 are shown being used withsystem 200 (e.g., with prosthetic valve assembly 202), describedhereinabove. However, it is to be noted that the techniques describedwith reference to FIGS. 18A-B may alternatively or additionally be usedto facilitate implantation of other prosthetic valves and/or prostheticvalve assemblies described herein, mutatis mutandis.

Typically, springs 520 and 530 provide similar functionality to springs484 and 504, described hereinabove, mutatis mutandis. For example, forsome applications, springs 520 and 530 provide an indication of a stateof the spring that is observable and recognizable using fluoroscopy.That is, the springs are configured to change shape in response to aforce applied to them, in a manner that is detectable and recognizableusing fluoroscopy. For some applications, springs 520 and 530 also alterthe relationship between (a) the length of tether 282 disposed betweeneyelet 222 and anchor 48 and (b) tension on the tether, e.g., asdescribed hereinabove with reference to springs 484 and 504, mutatismutandis.

Reference is again made to FIGS. 16, and 18A-B. Springs 484, 520 and 530are shown as helical springs. However, it is to be noted that each ofthese springs may have a shape other than a helix. For example, each ofthese springs may have a zigzag shape. For some applications, the use ofa spring that defines a repeating (e.g., oscillating) pattern such as ahelix or a zigzag facilitates fluoroscopic identification of the stateof the spring. For example, whereas a linear elastically-stretchablemember (e.g., a strip of elastic rubber) remains linear when stretched,the shape of a helical or zigzag spring changes as force increases.

Reference is made to FIGS. 19A-B, which are schematic illustrations of asystem 700 for facilitating delivery of a prosthetic valve body 702, inaccordance with some applications of the invention. System 700 comprisesa delivery tool 704 that comprises a distal housing 706, configured tohouse valve body 702 in a compressed state thereof, a proximal portion708, and a flexible longitudinal portion 710 (e.g., a catheter)therebetween. Proximal portion 708 typically comprises a handle 712.Housing 706 is configured to be transluminally advanced to the heart ofthe subject (e.g., as described herein, mutatis mutandis, while proximalportion 708 remains outside the body of the subject. Proximal portion708 (e.g., handle 712 thereof) comprises a force detector 716 thatdetects a force between (a) the proximal portion, and (b) housing 706and/or valve body 702 coupled thereto. Typically, force detector 716detects tension. That is, the force detector detects resistance of valvebody 702 to a proximally-directed force applied by tool 704 (e.g., whentool 704 is moved proximally).

Housing 706 is advanced through native valve 10 and into ventricle 8,and valve body 702 is partly advanced out of the housing, andautomatically expands toward an expanded state (FIG. 19A). Valve body702 is coupled to a plurality of tissue-engaging elements (e.g.,tissue-engaging legs) 714 that protrude radially out from the valve bodywhen exposed from housing 706. Tissue-engaging elements 714 areconfigured to engage leaflets 14 of the native valve, therebyfacilitating anchoring of the valve body.

Typically, system 700 is used for implantation of valve body 702 at anative valve at which a prosthetic valve support (e.g., an upstreamsupport) has already been delivered, and to which the valve body isintracorporeally coupled (e.g., as described elsewhere herein). Forexample, and as shown in FIGS. 19A-B, system 700 may be used to implantvalve body at native valve 10 after implantation of support 42 at thenative valve. As described with reference to FIGS. 1A-D, support 42 issecured against the upstream surface of native valve 10 by beinganchored, via tethers (e.g., longitudinal members 102), to ventricularmuscle tissue. (The tethers are not visible in FIGS. 19A-B.)

Pulling housing 706 and valve body 702 proximally (i.e., atrially) whiletissue-engaging elements 714 are protruding pushes the tissue-engagingelements against leaflets 14, reducing a height of a gap between thetissue-engaging elements and support 42, and sandwiching the leafletsagainst the support (FIG. 19B). Resistance to proximal movement of valvebody 702 (e.g., due to support 42 and leaflets 14) is detected anddisplayed by force detector 716. The operating physician is thereby ableto couple valve body 702 to support 42 (e.g., by fully deploying thevalve body within the opening defined by the support) while a desireddegree of tension is observed. The coupling of the valve body to thesupport fixes the degree of tension, such that leaflets 14 remainsandwiched, and the valve body remains secured to the native valve.

For some applications, alternatively or additionally to usingextracorporeal force detector 716, the force encountered bytissue-engaging elements 714 is observed using fluoroscopy (e.g., byobserving a shape and/or position of the tissue-engaging elements). Forsuch applications, the tissue-engaging elements are typically configuredto facilitate such observation, as described herein for various springs.For some applications, elements 714 are configured (e.g., shaped) todefine a loop, e.g., as described hereinabove for springs 504, mutatismutandis.

For some applications, valve body 702 is coupled via tethers to tissueanchors that are anchored to ventricular muscle tissue, as describedelsewhere herein. For some such applications, a spring couples the valvebody to each tissue anchor (e.g., as described with reference to FIGS.16-18B, mutatis mutandis). For some applications in which a springcouples the valve body to each tissue anchor, reducing the height of thegap automatically (and typically immediately) alters a force on thespring (e.g., when the valve body is locked to the tether beforereducing the height of the gap). For some applications in which a springcouples the valve body to each tissue anchor, reducing the height of thegap does not necessarily alter the force on the spring (e.g., when thevalve body is slidably couplable to the tether until after the height isreduced, and is subsequently locked to the tether. For example, tool 230and/or tool 460 may be used, mutatis mutandis, to measure and controltension and length of the tether until the valve body is locked to thetether.

It is to be noted that the above technique may be used for prostheticvalve assemblies in which the valve body is pre-coupled to the upstreamsupport, mutatis mutandis. For such applications, the proximal pullingforce is not a sandwiching force, but rather is a testing force,typically used in combination with another testing force, e.g., asdescribed hereinbelow, e.g., with reference to FIG. 20.

Reference is made to FIG. 20, which is a schematic illustration showingexamples in which force measurements described herein may be combined tofacilitate implantation of a prosthetic valve, in accordance with someapplications of the invention. Each apparatus and technique describedherein for measuring force (e.g., tension) is described in a particularcontext (e.g., with reference to a particular prosthetic valve assembly,prosthetic valve body, and/or support) for the purpose of clarity. It isto be understood that the apparatus and techniques described in onecontext may be used to measure force in another context (e.g., tofacilitate controlled implantation of a different prosthetic valveassembly, prosthetic valve body, and/or support), and may be combinedwith one or more of the other apparatus and/or techniques.

FIG. 20 shows examples of combinations of apparatus and techniquesdescribed herein, which include:

(1) Extracorporeal detection of tension on tethers (box 722). This isdescribed, for example, with reference to force detector 472 of tool 460of FIGS. 15A-C.

(2) Extracorporeal detection of atrially-directed force of valve-mountedtissue-engaging elements against tissue (e.g., leaflets or annulus) ofthe native valve (box 742). This is described, for example, withreference to FIGS. 19A-B.

(3) Extracorporeal detection of sandwiching force (box 720). That is,extracorporeal detection of the force of tissue-engaging elementscoupled to the valve body against the native valve tissue and/or theupstream support. This is described, for example, (a) with reference toFIGS. 19A-B, and (b) with reference to force detector 472 of tool 460(FIGS. 15A-C) being used to augment the apparatus and facilitate thetechniques described with reference to FIGS. 21A-B.

(4) Intracorporeal detection (observed using imaging) of tension ontethers (724). This is described, for example, with reference to thesprings described with reference to FIGS. 16, 17, and 18A-B.

(5) Intracorporeal detection (observed using imaging) ofatrially-directed force of valve-mounted tissue-engaging elementsagainst tissue (e.g., leaflets or annulus) of the native valve (box744). This is described, for example, with reference to FIGS. 19A-B.

(6) Intracorporeal detection (observed using imaging) of sandwichingforce (box 726). This is described, for example, with reference to oneor more of the springs described with reference to FIGS. 16, 17, and18A-B being used to augment the apparatus and facilitate the techniquesdescribed with reference to FIGS. 21A-B.

(7) Intracorporeal detection (observed using imaging) ofventricularly-directed force of the upstream support against the nativeannulus (box 728). For some applications, this is achieved by usingimaging (e.g., fluoroscopy) to extracorporeally observe intracorporealchanges in the shape of the upstream support (e.g., changes describedwith reference to FIGS. 8D-E, 14A-B, and/or 15A-B), in a similar mannerto that described for extracorporeally observing changes in the shape ofsprings (e.g., described with reference to FIGS. 16, 17, and 18A-B),mutatis mutandis.

It is hypothesized that combining two or more of the force-measurementtechniques described herein may provide synergistic benefits whenimplanting an implant (e.g., a prosthetic valve assembly, prostheticvalve body, and/or prosthetic valve support), so as to facilitatecontrolled implantation (box 730). The ability to control various forcesthat secure the implant allows, inter alia, the forces to be spread asdesired by the operating physician. For example, it may be desirable:

-   -   that tension is equally (or otherwise) distributed between the        tethers,    -   that tension on a given tether is optimized (discussed        hereinbelow),    -   that, during operation of the valve, resistance to a force that        pushes the valve body in an atrial direction (e.g., during        ventricular systole) is optimally balanced between the various        anchoring elements, such as between (a) tissue anchors 48 and        tethers coupled thereto and (b) other tissue-engaging elements        (e.g., tissue-engaging elements 714 (FIGS. 19A-B) or        tissue-engaging elements 580 (FIGS. 21A-B), thereby balancing        the anchoring forces between different tissue sites, and/or    -   that sandwiching forces are greater than, equal to, or less than        the tensile force provided by the tethers.

It is to be noted that the example combinations provided hereinabove areintended to be illustrative, and not limiting.

As described hereinabove, it may be desirable to that tension on a giventether is optimized. For example, it may be desirable that tension onthe given tether to be maximized within a tension range that is known tobe supported by (1) the tissue anchor to which the tether is coupled,and (2) the tissue to which the tissue anchor is anchored. For someapplications, subsequently to anchoring the tissue anchor, the operatingphysician applies a testing pulling force to the tissue anchor. Thetesting pulling force is used to confirm that the anchored tissue anchoris capable of supporting an overload tension that is greater than anexpected tension that it is expected that the anchor will encounterduring operation. The expected tension may be determined at least inpart based on possible ventricular blood pressure and thecross-sectional area of the lumen of the valve body.

For some applications, the testing pulling force is applied (e.g., viathe tether or via the anchor manipulator), and movement of the tissueanchor is observed using imaging, e.g., as described with reference toFIGS. 1A-B). For some applications, the testing pulling force is appliedwhile measuring tension using an extracorporeal force detector such asdetector 472 (FIGS. 15A-C), mutatis mutandis.

For some applications, the testing pulling force is applied by applyingtension to the tether, and the tension is measured using intracorporealsprings and fluoroscopy, as described hereinabove, mutatis mutandis. Itis to be noted that, for such applications, the same technique is used(1) to confirm that the anchored tissue anchor is capable of supportingthe overload tension, and (2) to facilitate the application of thetension (e.g., the anchoring tension) that will be fixed when thelocking member is locked to the tether.

As described hereinabove, it may be desirable that, during operation ofthe valve, resistance to a force that pushes the valve body in an atrialdirection (e.g., during ventricular systole) is optimally balancedbetween the various anchoring elements. For some applications, thefollowing technique is used:

(1) Anchor at least one tissue anchor coupled to a respective at leastone tether (e.g., within guide members).

(2) Advance a valve body that comprises at least one tissue-engagingelement (e.g., a tissue-engaging leg) over at least part of the tether(e.g., by advancing over a guide member), such that a length of thetether is disposed between the valve body and the tissue anchor.Examples of such tissue-engaging elements are described with referenceto FIGS. 19A-B and 21A-B. The valve body may or may not be pre-coupledto an upstream support.

(3) Apply a first tension to the tether (measured intracorporeally orextracorporeally).

(4) Apply proximal pulling force to the valve body such that thetissue-engaging element applies force against tissue of the nativevalve, such as leaflets and/or annulus. This pulling typicallyautomatically increases the tension on the tether.

(5) While applying the proximal pulling force, intracorporeally and/orextracorporeally measure (a) force of tissue-engaging element againsttissue, and (b) tension on the tether (e.g., the change in tension onthe tether caused by the proximal pulling.

(6) At least in part based on measurements (a) and (b) of step 5, adjustthe length of the tether disposed between the valve body and the tissueanchor, and/or lock the valve body to the tether (i.e., fix the lengthof the tether disposed between the valve body and the tissue anchor).

It is hypothesized that the above technique provides a prediction of theforce distribution between the various anchoring elements that willexist during operation of the prosthetic valve assembly (e.g., duringthe lifetime thereof). For example, the technique provides a predictionof force distribution between the ventricular anchors and thevalve-mounted tissue-engaging elements if/when atrially-directed forceincreases (e.g., as will be encountered during ventricular systoleand/or increases in systemic blood pressure). Based on this indication,the technique facilitates adjustment of this distribution, viaadjustment of the length of tethers disposed between the valve body andthe tissue anchors.

Reference is made to FIGS. 21A-B, which are schematic illustrations of aprosthetic valve assembly 552, in accordance with some applications ofthe invention. Prosthetic valve assembly 552 comprises (1) a prostheticvalve body 554, which comprises a first frame 556 (e.g., a wire frame),and is shaped to define a lumen therethrough, (2) an annular upstreamsupport 560, which comprises a second frame 562 (e.g., a wire frame), isshaped to define an opening through the upstream support, and isconfigured to be placed against an upstream surface (e.g., an atrialsurface) of native valve 10 (e.g., of an annulus thereof), and (3) aflexible sheet 564 that couples the first frame to the second frame.FIG. 21A shows assembly 552 in an expanded state thereof (e.g., in theabsence of external forces, such as if the assembly were resting on atable surface). In the expanded state of assembly 552 (and thereby ofbody 554), frame 556 of body 554 is generally cylindrical, and has adiameter d13. In the expanded state of assembly 552 (and thereby ofupstream support 560), frame 562 of support 560 is typically generallyannular, and has an outer perimeter 563 that has a diameter d14, whichis greater than diameter d13.

Assembly 552 comprises one or more tissue-engaging elements 580 (e.g.,legs) that protrude radially outward from valve body 554 so as to definea diameter d15, which is greater than diameter d13. Typically, and asshown in FIGS. 21A-B, frame 556 of body 554 is shaped to definetissue-engaging elements 580. Assembly 552 further comprises one or moretensioning elements (e.g., contraction wires) such as one or moretethers 582, a first portion (e.g., a distal end) of each tether beingcoupled to valve body 554, and a second portion of each tether beingcoupled (e.g., slidably coupled) to a portion of assembly 552 that isconfigured to be placed upstream of valve body 554. For example, and asshown, the second portion of each tether 582 may be slidably coupled toan upstream region of sheet 564. Alternatively or additionally, thesecond portion of each tether 582 may be slidably coupled to frame 562of support 560. For some applications, this is facilitated by frame 562being shaped to define one or more respective protrusions that protruderadially inward from the annular shape of the frame, to the site atwhich each tether 582 is shown in FIG. 21A passing through the sheet.

For some applications, except for (1) the presence of tissue-engagingelements 580 and tethers 582, and (2) the absence of eyelets 222,assembly 552 is identical to (e.g., comprises the same components as,and/or has identical functionality to) assembly 202, describedhereinabove. Identically-named components of system 202 and system 552are typically identical in structure and/or function.

For some applications, assembly 202 comprises tissue-engaging elements580 and/or tethers 582. For some applications, assembly 552 compriseseyelets 222 and/or locking members 262 for sliding over and locking toguide members.

Both support 560 of assembly 552 and support 210 of assembly 202 may beflat annular (e.g., as shown for support 210) or frustoconical (as shownfor support 560).

FIG. 21B shows assembly 552 being implanted. Following transluminaldelivery to native heart valve 10, valve body 554 is typically deployedfirst (i.e., before support 560), as shown in state A of FIG. 21B. Forsome applications, valve body is deployed sufficiently far into theventricle that tissue-engaging elements 580 can expand freely withoutinterfering with leaflets 14 of the native valve, and valve assembly issubsequently moved atrially into the position shown in state A of FIG.21B.

Subsequently, upstream support 560 is deployed, e.g., by a deliveryhousing 584 thereof being retracted (state B of FIG. 21B). Support 560becomes placed against the upstream (e.g., atrial) surface of nativevalve 10, such as against the annulus of the valve and/or against theupstream surface of native leaflets 14. Typically, immediatelysubsequently to deployment of body 554 and support 560, assembly 552 hasa total height d16 from a proximal end of support 560 to a distal end ofbody 554 (e.g., a height along an atrioventricular axis), and a distanced17 (e.g., a gap) measured along the height exists between a distal endof frame 562 and a proximal-most part of frame 556 (e.g.,tissue-engaging elements 580 defined by the frame).

Subsequently, tethers 582 are tensioned so as to draw support 560 andbody 554 closer to each other, thereby reducing the total height ofassembly 552 to height d18, and reducing the distance between the distalend of frame 562 and the proximal-most part of frame 556 to a distanced19 (state C of FIG. 21B). This moves body 554 and tissue-engagingelements 580 closer to leaflets 14, thereby sandwiching the leafletsbetween the tissue-engaging elements and support 560, and therebyanchoring assembly 552 at the native valve. Sheet 564 maintains fluidcommunication (e.g., sealed fluid communication) through assembly 202,while also allowing the described contraction of the assembly.Typically, this characteristic is due to sheet 564 having tensilestrength, but not compressive strength, and therefore rumpling whentethers 582 are tensioned.

Tensioning of tethers 582 may be accomplished by any suitable technique.For some applications, the tensioning is performed using control rods 86and locking members 110, e.g., as described with reference to FIGS.1C-D, mutatis mutandis. For some applications, the tensioning isperformed using reference-force tubes and locking members, e.g., asdescribed with reference to FIGS. 7B-8H, mutatis mutandis. For someapplications, support 560 comprises a ratchet mechanism that facilitatesthe tensioning by allowing only one-way movement of tether 582 throughthe support. For some applications, assembly 552 comprises a spoolmechanism for each tether, and tensioning is performed by rotating thespool mechanism.

For some applications, assembly 552 has a compressed state (e.g., fortransluminal delivery) in which the assembly defines an articulationzone between frames 556 and 562, e.g., as described hereinabove forassembly 202, mutatis mutandis.

For some application, one or more of the techniques describedhereinabove may be used to (1) control applied to tethers 582, and/or(2) facilitate intracorporeal measurement of tension on the tethers (andoptionally fluoroscopic detection of that measurement). For example,assembly 552 may comprise a tension spring midway along each tether 582,and/or may comprise a compression spring at the coupling point ofsupport 560 and the tether (e.g., between the support and a lockingmember 262 configured to lock a respective tether to the support).Alternatively or additionally, for applications in which the tensioningis performed using reference-force tubes and locking members (e.g., asdescribed with reference to FIGS. 7B-8H), tool 460 may be used, mutatismutandis, to extracorporeally detect the tension applied to tethers 582.

Reference is made to FIGS. 22A-B, which are schematic illustrations of aprosthetic valve assembly 602, comprising a prosthetic valve 603 havinga tubular valve body 604 that comprises an upstream portion 606, adownstream portion 608, and an elastic portion 610 disposed between theupstream portion and the downstream portion, in accordance with someapplications of the invention. Prosthetic valve 603 (e.g., valve body604 thereof) is shaped to define a continuous lumen through portions606, 610, and 608. Prosthetic valve 603 is configured to be implanted atnative valve 10 such that upstream portion 606 is disposed in atrium 6of the heart of the subject, and such that downstream portion 608 isdisposed in ventricle 8 of the heart of the subject. For example,prosthetic valve 603 may be coupled to a prosthetic valve support 612that has been previously placed against (e.g., coupled to) to the nativevalve, and that defines an opening. Support 612 may comprise (1) asupport described elsewhere herein (e.g., support 42 described withreference to FIGS. 1A-F and 19A-B, support 310 described with referenceto FIGS. 10A-B, and/or support 350, described with reference to FIGS.11A-B, and/or (2) a support described in U.S. Provisional Patentapplication 61/756,034 to HaCohen et al., from which the presentapplication claims priority, and which is incorporated herein byreference.

For some applications, and as shown in FIG. 22B, prosthetic valvesupport 612 comprises one or more tissue-engaging elements 618, anannular upstream support portion 620, and a flexible stabilizing member622, such as a stabilizing band, coupled to the tissue-engagingelements, and configured to form a ring that is shaped to define anopening therethrough. Tissue-engaging elements 618 may comprise, asshown in FIGS. 22A-B, clips configured to be coupled to leaflets 14 ofthe native valve.

Tubular valve body 604 typically comprises a frame 614, such as astent-like wire frame. As shown in FIG. 22A, prosthetic valve 603typically further comprises a covering 616, disposed over (e.g.,covering) an inner surface of frame 614, thereby providing a sealedlumen from an upstream end to a downstream end of the tubular valvebody. Typically, an excess of covering 616 is provided in the vicinityof elastic portion 610, so as to facilitate elastic stretching of theelastic portion.

Typically, prosthetic valve 603 comprises an expandable prostheticvalve, and is deployed such that it (1) expands within the openingdefined by upstream support portion 620 and/or the opening defined bystabilizing member 622, (2) applies a radially-expansive force againstthe upstream support portion and/or the stabilizing member, and (3)thereby becomes coupled thereto. Typically, and as shown in FIG. 22B,downstream portion 608 is expanded and coupled to stabilizing member 622before upstream portion 606 is expanded and coupled to upstream supportportion 620. While downstream portion 608 is coupled to member 622, andbefore upstream portion 606 is coupled to portion 620, elastic portion610 may be stretched and compressed e.g., such as by moving upstreamportion 606 further upstream and downstream. Such stretching andcompressing changes a length of prosthetic valve 603, and for someapplications, facilitates the coupling of a pre-determined portion ofthe prosthetic valve (e.g., of upstream portion 606) to upstream supportportion 620, irrespective, to some degree, of (a) a distance betweentissue-engaging elements 618 and upstream support portion 620, and/or(b) a dimension of native valve 10 (e.g., a length of leaflets 14). Forsome applications, such stretching and compressing adjusts a degree oftension of elastic portion 610, and may alternatively or additionallyfacilitate “tightening” of leaflets 14 against the implanted apparatus,such as drawing of the leaflets toward upstream support portion 620.

For some applications, prosthetic valve 603 may be used in combinationwith other apparatus and techniques described herein. For example, valvebody 604 may be substituted for another valve body described herein,mutatis mutandis, including valve bodies that are described herein asbeing intracorporeally coupled to an upstream support, and valve bodiesthat are described herein as being provided pre-coupled to an upstreamsupport (either directly, or via a flexible sheet).

Reference is made to FIGS. 23-24, which are schematic illustrations ofrespective systems for facilitating anchoring of a tissue anchor in theheart of a subject, in accordance with some applications of theinvention. Each system comprises a delivery tool that comprises (1) asteerable catheter configured to be transluminally advanced to the heartof the subject (e.g., via sheath 46), and (2) an obstructing elementdisposed at a longitudinal site of the catheter, and configured toextend laterally (e.g., radially) outward from the catheter so as toinhibit movement of at least the longitudinal site of the catheterthrough the heart valve by abutting tissue of the heart valve.

FIG. 23 shows a system 640, comprising a delivery tool 642 thatcomprises a catheter 644 and an obstructing element 646. Obstructingelement 646 is typically collapsible for transluminal delivery (e.g.,via sheath 46), and expandable in atrium 6 of the heart. For someapplications, element 646 is configured to expand automatically uponbecoming exposed from the distal end of sheath 46. Obstructing element646 is disposed at a longitudinal site 648 of catheter 644, and isdimensioned, when in the expanded state thereof, to not pass throughnative valve 10 (i.e., between leaflets 14 of the native valve). When adistal end 645 of the catheter is extended through native valve 10,obstructing element 646 abuts the atrial surface of the native valve(e.g., one or more leaflets, or the annulus), and thereby inhibitsmovement of at least longitudinal site 648 of the catheter from passingthrough the valve. Therefore, a known length d20 of catheter 644 (i.e.,the length between longitudinal site 648 and distal end 645) is disposeddownstream of the atrial surface of valve 10. Distal end 645 is therebyplaceable against ventricular tissue at ventricular sites that aredisposed at a distance from the atrial surface (e.g., from a portion ofthe atrial surface that element 646 abuts) that is generally equal tod20. A distal portion 652 of catheter 644, disposed distal tolongitudinal site 648, is typically steerable, so as to facilitateplacement of distal end 645 against many (e.g., any) ventricular sitethat is disposed at that distance from the atrial surface.

A tissue anchor 48 is advanced through catheter 644 using an anchormanipulator 650, and anchored to tissue at the ventricular site at whichdistal end 645 is disposed. Typically, little or none of anchor 48 ormanipulator 650 becomes exposed from distal end 645 during anchoring.

FIG. 24 shows a system 660, comprising a delivery tool 662 thatcomprises a catheter 664 and an obstructing element 666. Obstructingelement 666 is typically collapsible for transluminal delivery (e.g.,via sheath 46), and expandable in atrium 6 of the heart, and may beidentical to obstructing element 646, described hereinabove. For someapplications, element 666 is configured to expand automatically uponbecoming exposed from the distal end of sheath 46. Obstructing element666 is disposed at a longitudinal site 668 of catheter 664, and isdimensioned, when in the expanded state thereof, to not pass throughnative valve 10 (i.e., between leaflets 14 of the native valve). When adistal end 665 of the catheter is extended through native valve 10,obstructing element 666 abuts the atrial surface of the native valve(e.g., one or more leaflets, or the annulus), and thereby inhibitsmovement of at least longitudinal site 668 of the catheter from passingthrough the valve. Therefore, a known length d21 of catheter 664 (i.e.,the length between longitudinal site 668 and distal end 665) is disposeddownstream of the atrial surface of valve 10.

Length d21 of system 660 is typically shorter than length d20 of system640, and in contrast to system 640, for system 660, catheter 664 is notconfigured for distal end 665 to be placed against ventricular tissue.Rather, an anchor manipulator 670 advances tissue anchor 48 throughcatheter 664, out of the distal end 665, and toward a ventricular siteat which it anchors the tissue anchor. Typically, anchor manipulator 670is slidably coupled to catheter 664 such that a distal end of the anchormanipulator is slidable distally no more than a pre-determined distanced22 from longitudinal site 668 (and thereby no more than apre-determined distance from distal end 665 of catheter 664). Anchormanipulator 670 is thereby used to anchor 48 at a ventricular site thatis disposed at a distance from the atrial surface (e.g., from a portionof the atrial surface that element 666 abuts) that is generally equal tod22. Typically, anchor manipulator 670 (or at least a distal portion 672thereof that is exposable from distal end 665 of catheter 664) issteerable independently of catheter 664.

It is to be noted that, for systems 640 and 660, the distance from theatrial surface at which anchor 48 is anchored is generally equal, butnot necessarily exactly equal, to d20 or d22. For example, anchor 48 maybe anchored at a site that is closer to another portion of the atrialsurface than to the portion of the atrial surface that the obstructingelement abuts. Alternatively or additionally, curvature of the catheterand/or the anchor manipulator may result in a direct distance betweenthe atrial surface and the tissue anchor being smaller than d20 or d22.

Typically, anchor 48 is coupled to a tether, guide member, and/or otherlongitudinal member (e.g., as described hereinabove with reference toother systems). When the anchor driver is decoupled from the anchor andwithdrawn proximally, the tether extends proximally from the anchor(e.g., out of the body of the subject) so that an implant, such as aprosthetic valve, prosthetic valve support, and/or a prosthetic valveassembly (e.g., those described hereinabove) may be advanced therealongand/or locked thereto, e.g., as described hereinabove for other systems,mutatis mutandis. Because the distance between the tissue anchor and theatrial surface is known, for some applications the tether coupled to thetissue anchor may comprise fewer locking sites for locking to theimplant, a relatively shorter locking site, and/or only one lockingsite. It is hypothesized that this may provide the possibility of usingsimpler, smaller and/or more effective mechanisms to lock the implant tothe tether.

Reference is again made to FIGS. 7A-C, 8A-H, 9A-B, 15A-C, 16, 17, 18A-B,and 21A-B. The flexible sheets described hereinabove typically havetensile strength but very low compressive strength along thelongitudinal axis of assembly 202. Due to this characteristic, interalia, implant-control rod 246 is coupled (via mount 248) to assembly 202by being coupled to valve body 204, such that when the valve body ispushed distally, the valve body pulls upstream support 210 via sheet214. (It is hypothesized that it would be less effective for theimplant-control rod to be coupled to the support, because in such a casesheet 214 may rumple and the support may move toward the valve body,possibly reducing articulation at the articulation zone. Nevertheless,for applications in which such reduced articulation is in any casesufficient, the implant-control rod may be coupled to the support). Thischaracteristic of the flexible sheet also facilitates theheight-adjustment of assembly 552 and its sandwiching of the nativeleaflets by tensioning tethers 582.

Although each of the prosthetic valve assemblies is shown implanted in agenerally symmetrical state, it is to be noted that for someapplications this characteristic of the sheet facilitates asymmetricalimplantation. For example, the assembly may better conform to the nativeanatomy, and/or one tether of assembly 552 may be tensioned more thananother so as to alter the anchoring, sealing, and/or flowcharacteristics of the assembly, e.g., in response to the nativeanatomy.

For some applications it may be advantageous for the valve body to bedisposed at a particular rotational orientation within ventricle 8, andfor the upstream support to be disposed at a particular rotationalorientation within atrium 6. For example, for prosthetic valveassemblies such as assembly 202 that are tethered to ventricularanchors, it may be advantageous for each eyelet to be aligned with arespective anchor, and for the point at which each guide members passesthrough the upstream support to be aligned with a respective commissure.Alternatively or additionally, the upstream support may be geometricallyasymmetric, and a particular rotational orientation with respect toatrial tissue may be advantageous. (Examples of such upstream supportsare described in PCT patent application publication WO/2013/021374 toGross et. al, which is incorporated herein by reference.) Alternativelyor additionally, the upstream support may be asymmetric with respect torigidity (i.e., some regions of the support may be more rigid thanothers). Alternatively or additionally, it may be advantageous to placethe holes in sheet 214 through which tubes 260 pass in a particularrotational orientation with respect to the native valve.

For some applications, the sheet facilitates implantation of theupstream support in a different rotational position to its valve body,e.g., by twisting. For example, the upstream support may be implanted atmore than 5 degrees (e.g., more than 10 degrees, such as more than 20degrees) rotational offset with respect to the valve body.

Reference is again made to FIGS. 7A-14B, 16-18B, and 21A-B. For someapplications the first frame of the valve body is coupled to the secondframe of the upstream support by the sheet (e.g., generally only by thesheet) in the compressed state (e.g., assemblies 202, 302, 342 and 552)and/or in the expanded state (e.g., assemblies 202 and 552). As used inthe present application, including in the claims, (a) the first andsecond frames being “coupled by the sheet”, and/or (b) the sheet“coupling the first frame to the second frame”, do not includeapplications in which the frames are primarily and/or independentlycoupled to each other by a different means, and the covering extendsover both frames. For example, the first and second frames are not“coupled to each other by the sheet” (1) in assemblies 382, 402 and 422,in which the frames are provided pre-coupled directly to each other, or(2) in the expanded state of assemblies 302 and 342, in which the framesare intracorporeally coupled directly to each other.

For applications in which the first frame of the valve body is coupledto the second frame of the upstream support by the sheet, a gaptypically exists between the first frame and the second frame. For somesuch applications, no metallic structure is disposed within the gap.

For some applications (including some applications in which the firstand second frames are coupled independently of the sheet), the flexiblesheet comprises, in addition to the sheet-like structure, one or moreflexible longitudinal members, such as metallic or polymer wires (e.g.,embedded within or attached to a surface of the sheet-like structure).These flexible longitudinal members may provide a small amount ofrigidity to the sheet without detracting from the general nature of thesheet. For example, the flexible longitudinal members may facilitateopening of the sheet during deployment of the prosthetic valve assembly.

It is to be noted that for applications in which the first and secondframes are coupled by the sheet, even when the sheet comprises flexiblelongitudinal members that are metallic wires, the frame of the valvebody and the frame of the upstream support are typically distinct fromeach other, and can be considered to be coupled to each other by thesheet (e.g., generally only by the sheet).

For some applications, within the total height of the prosthetic valveassembly, a distance exists within which no rigid and/or metallicstructure is disposed. For example, for assembly 552, typically no rigidand/or metallic structure is disposed within distance d17 and/ordistance d19. It is to be noted that a similar distance exists forassembly 202 between frames 212 and 206 (e.g., when implanted; see FIGS.8F-G). For some applications, for assembly 552, only sheet 564 andtethers 582 are disposed within distances d17 and d19. However, for someapplications, tissue-engaging elements 580 extend proximally towardframe 562 such that the distance in which no rigid and/or metallicstructure is disposed is reduced and/or absent (e.g., when tethers 582are tensioned).

Reference is again made to FIGS. 1A-F, 3A-C, 6 and 7A-8H. For someapplications of the invention, tissue anchor 48 and/or the guide membercoupled thereto (e.g., guide member 56, guide member 256, and/or thecomponents thereof) are included as components of the providedapparatus. That is, they are typically provided with the prostheticvalve assembly. For some applications of the invention, the tissueanchor and/or the guide member coupled thereto are not included ascomponents of the provided apparatus (e.g., they are obtainedseparately).

It will be understood that, although the terms “first, “second,” etc.may be used in the present application (including the specification andthe claims) to describe various elements and/or directions, these termsshould not be limiting. These terms are only used to distinguish oneelement and/or direction from another. Thus, a “first” element describedherein could also be termed a “second” element without departing fromthe teachings of the present disclosure.

As used in the present application, including in the claims, a “centrallongitudinal axis” of a structure (e.g., an elongate structure) is theset of all centroids of transverse cross-sectional sections of thestructure along the structure. Thus the cross-sectional sections arelocally perpendicular to the central longitudinal axis, which runs alongthe structure. (If the structure is circular in cross-section, thecentroids correspond with the centers of the circular cross-sectionalsections.)

It will be appreciated by persons skilled in the art that the presentinvention is not limited to what has been particularly shown anddescribed hereinabove. Rather, the scope of the present inventionincludes both combinations and subcombinations of the various featuresdescribed hereinabove, as well as variations and modifications thereofthat are not in the prior art, which would occur to persons skilled inthe art upon reading the foregoing description.

The invention claimed is:
 1. Apparatus for use at a native valve of aheart of a subject, the apparatus comprising: a prosthetic valve,comprising: a valve body, comprising a tubular frame and a plurality ofprosthetic leaflets arranged to facilitate upstream-to-downstream fluidflow through the prosthetic valve; an upstream support, comprising asecond frame that is distinct from the tubular frame; and a flexiblesheet that flexibly couples the upstream support to the valve body; anda delivery tool comprising, at a distal portion of the delivery tool, afirst housing and a second housing, wherein: in a delivery configurationof the apparatus, the distal portion of the delivery tool is dimensionedfor transluminal advancement to the heart, and the prosthetic valve isin a compressed state in which: the second frame and the tubular frameare arranged in series within the delivery tool, with the tubular framedistal to the second frame, at least part of the tubular frame iscompressed within the first housing, at least part of the second frameis compressed within the second housing, and at least a part of thesheet extends between the tubular frame and the second frame; and theprosthetic valve is deployable from the delivery tool by distancing thefirst housing front the second housing, such that the prosthetic valveautomatically expands into an expanded state in which the valve body isshaped to fit within the native valve, and the second frame is shaped tobe placed against an upstream surface of the native valve.
 2. Theapparatus according to claim 1, wherein, in the delivery configuration,at least the part of the sheet is exposed between the first housing andthe second housing.
 3. The apparatus according to claim 1, wherein, inthe delivery configuration, the sheet articulatably couples the tubularframe to the second frame.
 4. The apparatus according to claim 1,wherein, in the delivery configuration, the apparatus defines anarticulation zone in which (a) at least the part of the sheet isdisposed, and (b) neither the tubular frame nor the second frame isdisposed, and about which the valve body and the upstream support arearticulatable with respect to each other.
 5. The apparatus according toclaim 4, wherein the delivery tool further comprises a flexible controlrod assembly via which the first housing is articulatably coupled to thesecond housing.
 6. The apparatus according to claim 1, wherein, in theexpanded state, the sheet is frustoconical.
 7. The apparatus accordingto claim 1, wherein, in the expanded state, the second frame is annular.8. The apparatus according to claim 1, wherein, in the compressed state,the second frame is tubular.
 9. The apparatus according to claim 1,wherein: in the compressed state, the second frame has a first end, anda second end that is closer to the tubular frame than is the first end,and the prosthetic valve is configured such that when the prostheticvalve automatically expands into the expanded state, the first endexpands more than the second end.
 10. The apparatus according to claim1, wherein at least one side of the tubular frame and at least one sideof the second frame are covered with a covering, and the part of thesheet is defined by, a portion of the covering that extends between thetubular frame and the second frame.
 11. The apparatus according to claim10, wherein the covering is disposed on a tissue-facing side of thesecond frame, the tissue-facing side being oriented to be placed againstthe upstream surface of the native valve.
 12. The apparatus according toclaim 10, wherein, in the compressed state, the second frame is tubular,and the covering is disposed on an outer surface of the second frame.13. The apparatus according to claim 12, wherein the covering lines aninner surface of the tubular frame.
 14. The apparatus according to claim1, wherein the prosthetic valve is configured such that, upon deploymentfrom the delivery tool, the second frame becomes annular by deflectingwith respect to the valve body.